Received date: 22 Jun 2013
Accepted date: 05 Aug 2013
Published date: 01 Oct 2013
Copyright
RasGRP proteins are activators of Ras and other related small GTPases by the virtue of functioning as guanine nucleotide exchange factors (GEFs). In vertebrates, four RasGRP family members have been described. RasGRP-1 through-4 share many structural domains but there are also subtle differences between each of the different family members. Whereas SOS RasGEFs are ubiquitously expressed, RasGRP proteins are expressed in distinct patterns, such as in different cells of the hematopoietic system and in the brain. Most studies have concentrated on the role of RasGRP proteins in the development and function of immune cell types because of the predominant RasGRP expression profiles in these cells and the immune phenotypes of mice deficient for Rasgrp genes. However, more recent studies demonstrate that RasGRPs also play an important role in tumorigenesis. Examples are skin- and hematological-cancers but also solid malignancies such as melanoma or prostate cancer. These novel studies bring up many new and unanswered questions related to the molecular mechanism of RasGRP-driven oncogenesis, such as new receptor systems that RasGRP appears to respond to as well as regulatory mechanisms for RasGRP expression that appear to be perturbed in these cancers. Here we will review some of the known aspects of RasGRP biology in lymphocytes and will discuss the exciting new notion that RasGRP Ras exchange factors play a role in oncogenesis downstream of various growth factor receptors.
Olga KSIONDA , Andre LIMNANDER , Jeroen P. ROOSE . RasGRP Ras guanine nucleotide exchange factors in cancer[J]. Frontiers in Biology, 2013 , 8(5) : 508 -532 . DOI: 10.1007/s11515-013-1276-9
| 1 |
Abel E L, Angel J M, Kiguchi K, DiGiovanni J (2009). Multi-stage chemical carcinogenesis in mouse skin: fundamentals and applications. Nat Protoc, 4(9): 1350–1362
|
| 2 |
Adachi R, Krilis S A, Nigrovic P A, Hamilton M J, Chung K, Thakurdas S M, Boyce J A, Anderson P, Stevens R L (2012). Ras guanine nucleotide-releasing protein-4 (RasGRP4) involvement in experimental arthritis and colitis. J Biol Chem, 287(24): 20047–20055
|
| 3 |
Ahearn I M, Haigis K, Bar-Sagi D, Philips M R (2012). Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol, 13(1): 39–51
|
| 4 |
Ahuja H, Foti A, Bar-Eli M, Cline M (1990). The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing. Blood, 75: 1684–1690
|
| 5 |
Aiba Y, Oh-hora M, Kiyonaka S, Kimura Y, Hijikata A, Mori Y, Kurosaki T (2004). Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation. Proc Natl Acad Sci USA, 101(47): 16612–16617
|
| 6 |
Aifantis I, Raetz E, Buonamici S (2008). Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat Rev Immunol, 8(5): 380–390
|
| 7 |
Alberola-Ila J, Hogquist K A, Swan K A, Bevan M J, Perlmutter R M (1996). Positive and negative selection invoke distinct signaling pathways. J Exp Med, 184(1): 9–18
|
| 8 |
Balgobind B V, Van Vlierberghe P, van den Ouweland A M W, Beverloo H B, Terlouw-Kromosoeto J N R, van Wering E R, Reinhardt D, Horstmann M, Kaspers G J L, Pieters R, Zwaan C M, Van den Heuvel-Eibrink M M, Meijerink J P (2008). Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. Blood, 111(8): 4322-4328
|
| 9 |
Barata J T, Cardoso A A, Boussiotis V A (2005). Interleukin-7 in T-cell acute lymphoblastic leukemia: an extrinsic factor supporting leukemogenesis? Leuk Lymphoma, 46(4): 483-495
|
| 10 |
Barata J T, Keenan T D, Silva A, Nadler L M, Boussiotis V A, Cardoso A A (2004a). Common gamma chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia. Haematologica, 89(12): 1459-1467
|
| 11 |
Barata J T, Silva A, Brandao J G, Nadler L M, Cardoso A A, Boussiotis V A (2004b). Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells. J Exp Med, 200(5): 659-669
|
| 12 |
Beaulieu N, Zahedi B, Goulding R E, Tazmini G, Anthony K V, Omeis S L, de Jong D R, Kay R J (2007). Regulation of RasGRP1 by B cell antigen receptor requires cooperativity between three domains controlling translocation to the plasma membrane. Mol Biol Cell, 18(8): 3156-3168
|
| 13 |
Bell J J, Bhandoola A (2008). The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature, 452(7188): 764-767
|
| 14 |
Benschop R J, Cambier J C (1999). B cell development: signal transduction by antigen receptors and their surrogates. Curr Opin Immunol, 11(2): 143-151
|
| 15 |
Bergmeier W, Goerge T, Wang H W, Crittenden J R, Baldwin A C W, Cifuni S M, Housman D E, Graybiel A M, Wagner D D (2007). Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III. J Clin Invest, 117(6): 1699-1707
|
| 16 |
Berquam-Vrieze K E, Nannapaneni K, Brett B T, Holmfeldt L, Ma J, Zagorodna O, Jenkins N A, Copeland N G, Meyerholz D K, Knudson C M, Mullighan C G, Scheetz T E, Dupuy A J (2011). Cell of origin strongly influences genetic selection in a mouse model of T-ALL. Blood, 118(17): 4646-4656
|
| 17 |
Bivona T G, Pérez De Castro I, Ahearn I M, Grana T M, Chiu V K, Lockyer P J, Cullen P J, Pellicer A, Cox A D, Philips M R (2003). Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature, 424(6949): 694-698
|
| 18 |
Bos J L, Rehmann H, Wittinghofer A (2007). GEFs and GAPs: critical elements in the control of small G proteins. Cell, 129(5): 865-877
|
| 19 |
Botelho R J, Harrison R E, Stone J C, Hancock J F, Philips M R, Jongstra-Bilen J, Mason D, Plumb J, Gold M R, Grinstein S (2009). Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis. J Biol Chem, 284(42): 28522-28532
|
| 20 |
Boykevisch S, Zhao C, Sondermann H, Philippidou P, Halegoua S, Kuriyan J, Bar-Sagi D (2006). Regulation of ras signaling dynamics by Sos-mediated positive feedback. Curr Biol, 16(21): 2173-2179
|
| 21 |
Brodie C, Steinhart R, Kazimirsky G, Rubinfeld H, Hyman T, Ayres J N, Hur G M, Toth A, Yang D, Garfield S H, Stone J C, Blumberg P M (2004). PKCdelta associates with and is involved in the phosphorylation of RasGRP3 in response to phorbol esters. Mol Pharmacol, 66(1): 76-84
|
| 22 |
Cambier J C, Gauld S B, Merrell K T, Vilen B J (2007). B-cell anergy: from transgenic models to naturally occurring anergic B cells? Nat Rev Immunol, 7(8): 633-643
|
| 23 |
Carbo C, Duerschmied D, Goerge T, Hattori H, Sakai J, Cifuni S M, White G C 2nd, Chrzanowska-Wodnicka M, Luo H R, Wagner D D (2010). Integrin-independent role of CalDAG-GEFI in neutrophil chemotaxis. J Leukoc Biol, 88(2): 313-319
|
| 24 |
Chakraborty A K, Roose J P (2013). Biochemical heterogeneity and developmental varieties in T-cell leukemia. Cell Cycle, 12(10): 1480-1481
|
| 25 |
Chan S M, Weng A P, Tibshirani R, Aster J C, Utz P J (2007). Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia. Blood, 110(1): 278-286
|
| 26 |
Chang L, Karin M (2001). Mammalian MAP kinase signalling cascades. Nature, 410(6824): 37-40
|
| 27 |
Chiarini F, Falà F, Tazzari P L, Ricci F, Astolfi A, Pession A, Pagliaro P, McCubrey J A, Martelli A M (2009). Dual inhibition of class IA phosphatidylinositol 3-kinase and mammalian target of rapamycin as a new therapeutic option for T-cell acute lymphoblastic leukemia. Cancer Res, 69(8): 3520-3528
|
| 28 |
Chung J B, Silverman M, Monroe J G (2003). Transitional B cells: step by step towards immune competence. Trends Immunol, 24(6): 343-349
|
| 29 |
Cifuni S M, Wagner D D, Bergmeier W (2008). CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets. Blood, 112(5): 1696-1703
|
| 30 |
Clyde-Smith J, Silins G, Gartside M, Grimmond S, Etheridge M, Apolloni A, Hayward N, Hancock J F (2000). Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor. J Biol Chem, 275(41): 32260-32267
|
| 31 |
Corey S J, Minden M D, Barber D L, Kantarjian H, Wang J C Y, Schimmer A D (2007). Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer, 7(2): 118-129
|
| 32 |
Coughlin J J, Stang S L, Dower N A, Stone J C (2005). RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor-Ras signaling. J Immunol (Baltimore, Md: 1950) 175(11): 7179-7184
|
| 33 |
Coustan-Smith E, Mullighan C G, Onciu M, Behm F G, Raimondi S C, Pei D, Cheng C, Su X, Rubnitz J E, Basso G, Biondi A, Pui C H, Downing J R, Campana D (2009). Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol, 10(2): 147-156
|
| 34 |
Crittenden J R, Bergmeier W, Zhang Y, Piffath C L, Liang Y, Wagner D D, Housman D E, Graybiel A M (2004). CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med, 10(9): 982-986
|
| 35 |
Dail M, Li Q, McDaniel A, Wong J, Akagi K, Huang B, Kang H C, Kogan S C, Shokat K, Wolff L, Braun B S, Shannon K (2010). Mutant Ikzf1, KrasG12D, and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents. Proc Natl Acad Sci USA, 107(11): 5106-5111
|
| 36 |
Dal Porto J M, Gauld S B, Merrell K T, Mills D, Pugh-Bernard A E, Cambier J (2004). B cell antigen receptor signaling 101. Mol Immunol, 41(6-7): 599-613
|
| 37 |
Daniels M A, Teixeiro E, Gill J, Hausmann B, Roubaty D, Holmberg K, Werlen G, Holländer G A, Gascoigne N R J, Palmer E (2006). Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling. Nature, 444(7120): 724-729
|
| 38 |
Das J, Ho M, Zikherman J, Govern C, Yang M, Weiss A, Chakraborty A K, Roose J P (2009). Digital signaling and hysteresis characterize ras activation in lymphoid cells. Cell, 136(2): 337-351
|
| 39 |
de la Luz Sierra M, Sakakibara S, Gasperini P, Salvucci O, Jiang K, McCormick P J, Segarra M, Stone J, Maric D, Zhu J, Qian X, Lowy D R, Tosato G (2010). The transcription factor Gfi1 regulates G-CSF signaling and neutrophil development through the Ras activator RasGRP1. Blood, 115(19): 3970-3979
|
| 40 |
DeAngelo D J (2006). A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia (T-ALL) and other leukemias. J Clin Oncol, 24(18 Suppl): 6585
|
| 41 |
DeFranco A L (2000). B-cell activation 2000. Immunol Rev, 176: 5-9
|
| 42 |
Diaz-Flores E,, Hana Goldschmidt, Philippe Depeille, Victor Ng, Kimberly Krisman, Michael Crone, Michael R. Burgess, Olusegun Williams, BenjaminHouseman, Kevan Shokat, et al. (2013). PLCγ and PI3 kinase link cytokine stimulation to ERK activation in primary hematopoietic cells expressing normal and oncogenic Kras. Science Signaling, (In press)
|
| 43 |
Diehn M, Alizadeh A A, Rando O J, Liu C L, Stankunas K, Botstein D, Crabtree G R, Brown P O (2002). Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proc Natl Acad Sci USA, 99(18): 11796-11801
|
| 44 |
Diez F R, Garrido A A, Sharma A, Luke C T, Stone J C, Dower N A, Cline J M, Lorenzo P S (2009). RasGRP1 transgenic mice develop cutaneous squamous cell carcinomas in response to skin wounding: potential role of granulocyte colony-stimulating factor. Am J Pathol, 175(1): 392-399
|
| 45 |
Dower N A, Stang S L, Bottorff D A, Ebinu J O, Dickie P, Ostergaard H L, Stone J C (2000). RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nat Immunol, 1(4): 317-321
|
| 46 |
Dührsen U, Stahl J, Gough N M (1990). In vivo transformation of factor-dependent hemopoietic cells: role of intracisternal A-particle transposition for growth factor gene activation. EMBO J, 9(4): 1087-1096
|
| 47 |
Ebinu J O, Bottorff D A, Chan E Y, Stang S L, Dunn R J, Stone J C (1998). RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. Science, 280(5366): 1082-1086
|
| 48 |
Ebinu J O, Stang S L, Teixeira C, Bottorff D A, Hooton J, Blumberg P M, Barry M, Bleakley R C, Ostergaard H L, Stone J C (2000). RasGRP links T-cell receptor signaling to Ras. Blood, 95(10): 3199-3203
|
| 49 |
Emanuel P D, Bates L J, Castleberry R P, Gualtieri R J, Zuckerman K S (1991). Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood, 77(5): 925-929
|
| 50 |
Feldman B J, Feldman D (2001). The development of androgen-independent prostate cancer. Nat Rev Cancer, 1(1): 34-45
|
| 51 |
Ferrando A A, Neuberg D S, Staunton J, Loh M L, Huard C, Raimondi S C, Behm F G, Pui C H, Downing J R, Gilliland D G, Lander E S, Golub T R, Look A T (2002). Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell, 1(1): 75-87
|
| 52 |
Feske S (2007). Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol, 7(9): 690-702
|
| 53 |
Friday B B, Adjei A A (2005). K-ras as a target for cancer therapy. Biochimica et Biophysica Acta (BBA) -. Rev Can, 1756: 127-144
|
| 54 |
Fuller D M, Zhu M, Song X, Ou-Yang C W, Sullivan S A, Stone J C, Zhang W (2012). Regulation of RasGRP1 function in T cell development and activation by its unique tail domain. PLoS ONE, 7(6): e38796
|
| 55 |
Ghandour H, Cullere X, Alvarez A, Luscinskas F W, Mayadas T N (2007). Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion. Blood, 110(10): 3682-3690
|
| 56 |
Gifford J L, Walsh M P, Vogel H J (2007). Structures and metal-ion-binding properties of the Ca2+-binding helix-loop-helix EF-hand motifs. Biochem J, 405(2): 199-221
|
| 57 |
Golec D P, Dower N A, Stone J C, Baldwin T A (2013). RasGRP1, but not RasGRP3, is required for efficient thymic β-selection and ERK activation downstream of CXCR4. PLoS ONE, 8(1): e53300
|
| 58 |
Goodnow C C, Crosbie J, Jorgensen H, Brink R A, Basten A (1989). Induction of self-tolerance in mature peripheral B lymphocytes. Nature, 342(6248): 385-391
|
| 59 |
Grabarek Z (2006). Structural basis for diversity of the EF-hand calcium-binding proteins. J Mol Biol, 359(3): 509-525
|
| 60 |
Grabher C, von Boehmer H, Look A T (2006). Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer, 6(5): 347-359
|
| 61 |
Graux C, Cools J, Michaux L, Vandenberghe P, Hagemeijer A (2006). Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia, 20(9): 1496-1510
|
| 62 |
Grisendi S, Mecucci C, Falini B, Pandolfi P P (2006). Nucleophosmin and cancer. Nat Rev Cancer, 6(7): 493-505
|
| 63 |
Guilbault B, Kay R J (2004). RasGRP1 sensitizes an immature B cell line to antigen receptor-induced apoptosis. J Biol Chem, 279(19): 19523-19530
|
| 64 |
Gutierrez A, Sanda T, Grebliunaite R, Carracedo A, Salmena L, Ahn Y, Dahlberg S, Neuberg D, Moreau L A, Winter S S, Larson R, Zhang J, Protopopov A, Chin L, Pandolfi P P, Silverman L B, Hunger S P, Sallan S E, Look A T (2009). High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood, 114(3): 647-650
|
| 65 |
Hartzell C, Ksionda O, Lemmens E, Coakley K, Yang M, Dail M, Harvey R C, Govern C, Bakker J, Lenstra T L, Ammon K, Boeter A, Winter S S, Loh M, Shannon K, Chakraborty A K, Wabl M, Roose J P (2013). Dysregulated RasGRP1 responds to cytokine receptor input in T cell leukemogenesis. Sci Signal, 6(268): ra21
|
| 66 |
Hertz M, Nemazee D (1997). BCR ligation induces receptor editing in IgM+IgD- bone marrow B cells in vitro. Immunity, 6(4): 429-436
|
| 67 |
Izquierdo M, Downward J, Graves J D, Cantrell D A (1992). Role of protein kinase C in T-cell antigen receptor regulation of p21ras: evidence that two p21ras regulatory pathways coexist in T cells. Mol Cell Biol, 12(7): 3305-3312
|
| 68 |
Janas M L, Turner M (2011). Interaction of Ras with P110 is required for thymic-selection in the mouse. J Immunol (Baltimore, Md: 1950) 187: 4667-4675
|
| 69 |
Johnson J E, Goulding R E, Ding Z, Partovi A, Anthony K V, Beaulieu N, Tazmini G, Cornell R B, Kay R J (2007). Differential membrane binding and diacylglycerol recognition by C1 domains of RasGRPs. Biochem J, 406(2): 223-236
|
| 70 |
Jun J E,, Ignacio Rubio, Roose J P (2013). Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells. Fronit Immunol, (In press)
|
| 71 |
Kawamura M, Ohnishi H, Guo S X, Sheng X M, Minegishi M, Hanada R, Horibe K, Hongo T, Kaneko Y, Bessho F, Yanagisawa M, Sekiya T, Hayashi Y (1999). Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia. Leuk Res, 23(2): 115-126
|
| 72 |
Kawasaki H, Springett G M, Toki S, Canales J J, Harlan P, Blumenstiel J P, Chen E J, Bany I A, Mochizuki N, Ashbacher A, Matsuda M, Housman D E, Graybiel A M (1998). A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci USA, 95(22): 13278-13283
|
| 73 |
Khandanpour C, Phelan J D, Vassen L, Schütte J, Chen R, Horman S R, Gaudreau M C, Krongold J, Zhu J, Paul W E, Dührsen U, Göttgens B, Grimes H L, Möröy T (2013). Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer Cell, 23(2): 200-214
|
| 74 |
Kim R, Trubetskoy A, Suzuki T, Jenkins N A, Copeland N G, Lenz J (2003). Genome-based identification of cancer genes by proviral tagging in mouse retrovirus-induced T-cell lymphomas. J Virol, 77(3): 2056-2062
|
| 75 |
Klein L, Hinterberger M, Wirnsberger G, Kyewski B (2009). Antigen presentation in the thymus for positive selection and central tolerance induction. Nat Rev Immunol, 9(12): 833-844
|
| 76 |
Klinger M B, Guilbault B, Goulding R E, Kay R J (2005). Deregulated expression of RasGRP1 initiates thymic lymphomagenesis independently of T-cell receptors. Oncogene, 24(16): 2695-2704
|
| 77 |
Knudsen B S, Edlund M (2004). Prostate cancer and the met hepatocyte growth factor receptor. Adv Cancer Res, 91: 31-67
|
| 78 |
Koike K, Matsuda K (2008). Recent advances in the pathogenesis and management of juvenile myelomonocytic leukaemia. Br J Haematol, 141(5): 567-575
|
| 79 |
Kortum R L, Rouquette-Jazdanian A K, Samelson L E (2013). Ras and extracellular signal-regulated kinase signaling in thymocytes and T cells. Trends Immunol, 34(6): 1-10
|
| 80 |
Kortum R L, Sommers C L, Alexander C P, Pinski J M, Li W, Grinberg A, Lee J, Love P E, Samelson L E (2011). Targeted Sos1 deletion reveals its critical role in early T-cell development. Proc Natl Acad Sci USA, 108(30): 12407-12412
|
| 81 |
Kortum R L, Sommers C L, Pinski J M, Alexander C P, Merrill R K, Li W, Love P E, Samelson L E (2012). Deconstructing Ras signaling in the thymus. Mol Cell Biol, 32(14): 2748-2759
|
| 82 |
Kremer K N, Kumar A, Hedin K E (2011). G i2 and ZAP-70 mediate RasGRP1 membrane localization and activation of SDF-1-induced T cell functions. J Immunol (Baltimore, Md: 1950), 187: 3177-3185
|
| 83 |
Kurosaki T (1999). Genetic analysis of B cell antigen receptor signaling. Annu Rev Immunol, 17(1): 555-592
|
| 84 |
Lam K P, Kühn R, Rajewsky K (1997). In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell, 90(6): 1073-1083
|
| 85 |
Lauchle J O, Kim D, Le D T, Akagi K, Crone M, Krisman K, Warner K, Bonifas J M, Li Q, Coakley K M, Diaz-Flores E, Gorman M, Przybranowski S, Tran M, Kogan S C, Roose J P, Copeland N G, Jenkins N A, Parada L, Wolff L, Sebolt-Leopold J, Shannon K (2009). Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras. Nature, 461(7262): 411-414
|
| 86 |
Lee J R, Koretzky G A (1998). Extracellular signal-regulated kinase-2, but not c-Jun NH2-terminal kinase, activation correlates with surface IgM-mediated apoptosis in the WEHI 231 B cell line. J Immunol, 161(4): 1637-1644
|
| 87 |
Lee M J, Ye A S, Gardino A K, Heijink A M, Sorger P K, MacBeath G, Yaffe M B (2012). Sequential application of anticancer drugs enhances cell death by rewiring apoptotic signaling networks. Cell, 149(4): 780-794
|
| 88 |
Lee S H, Yun S, Lee J, Kim M J, Piao Z-H, Jeong M, Chung J W, Kim T-D, Yoon S R, Greenberg P D, Choi I (2009). RasGRP1 is required for human NK cell function. J Immunol (Baltimore, Md: 1950) 183: 7931-7938
|
| 89 |
Li L, Yang Y, Wong G W, Stevens R L (2003). Mast cells in airway hyporesponsive C3H/HeJ mice express a unique isoform of the signaling protein Ras guanine nucleotide releasing protein 4 that is unresponsive to diacylglycerol and phorbol esters. J Immunol (Baltimore, Md: 1950), 171: 390-397
|
| 90 |
Limnander A, Depeille P, Freedman T S, Liou J, Leitges M, Kurosaki T, Roose J P, Weiss A (2011). STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development. Nat Immunol, 12(5): 425-433
|
| 91 |
Limnander A, Weiss A (2011). Ca-dependent Ras/Erk signaling mediates negative selection of autoreactive B cells. Small GTPases, 2(5): 282-288
|
| 92 |
Lorenzo P S, Beheshti M, Pettit G R, Stone J C, Blumberg P M (2000). The guanine nucleotide exchange factor RasGRP is a high-affinity target for diacylglycerol and phorbol esters. Mol Pharmacol, 57(5): 840-846
|
| 93 |
Lorenzo P S, Kung J W, Bottorff D A, Garfield S H, Stone J C, Blumberg P M (2001). Phorbol esters modulate the Ras exchange factor RasGRP3. Cancer Res, 61(3): 943-949
|
| 94 |
Luke C T, Oki-Idouchi C E, Cline J M, Lorenzo P S (2007). RasGRP1 overexpression in the epidermis of transgenic mice contributes to tumor progression during multistage skin carcinogenesis. Cancer Res, 67(21): 10190-10197
|
| 95 |
Maser R S, Choudhury B, Campbell P J, Feng B, Wong K K, Protopopov A, O’Neil J, Gutierrez A, Ivanova E, Perna I, Lin E, Mani V, Jiang S, McNamara K, Zaghlul S, Edkins S, Stevens C, Brennan C, Martin E S, Wiedemeyer R, Kabbarah O, Nogueira C, Histen G, Aster J, Mansour M, Duke V, Foroni L, Fielding A K, Goldstone A H, Rowe J M, Wang Y A, Look A T, Stratton M R, Chin L, Futreal P A, DePinho R A (2007). Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature, 447(7147): 966-971
|
| 96 |
Melamed D, Benschop R J, Cambier J C, Nemazee D (1998). Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection. Cell, 92(2): 173-182
|
| 97 |
Mikkers H, Allen J, Knipscheer P, Romeijn L, Hart A, Vink E, Berns A, Romeyn L (2002). High-throughput retroviral tagging to identify components of specific signaling pathways in cancer. Nat Genet, 32(1): 153-159
|
| 98 |
Mor A, Philips M R (2006). Compartmentalized Ras/MAPK signaling. Annu Rev Immunol, 24(1): 771-800
|
| 99 |
Navarro M N, Goebel J, Feijoo-Carnero C, Morrice N, Cantrell D A (2011). Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes. Nat Immunol, 12(4): 352-361
|
| 100 |
Norment A M, Bogatzki L Y, Klinger M, Ojala E W, Bevan M J, Kay R J (2003). Transgenic expression of RasGRP1 induces the maturation of double-negative thymocytes and enhances the production of CD8 single-positive thymocytes. J Immunol (Baltimore, Md: 1950), 170: 1141-1149
|
| 101 |
Oh-hora M, Johmura S, Hashimoto A, Hikida M, Kurosaki T (2003). Requirement for Ras guanine nucleotide releasing protein 3 in coupling phospholipase C-gamma2 to Ras in B cell receptor signaling. J Exp Med, 198(12): 1841-1851
|
| 102 |
Oki T, Kitaura J, Watanabe-Okochi N, Nishimura K, Maehara A, Uchida T, Komeno Y, Nakahara F, Harada Y, Sonoki T,βHarada H,βKitamura T (2011). Aberrant expression of RasGRP1 cooperates with gain-of-function NOTCH1 mutations in T-cell leukemogenesis. Leukemia
|
| 103 |
Oki-Idouchi C E, Lorenzo P S (2007). Transgenic overexpression of RasGRP1 in mouse epidermis results in spontaneous tumors of the skin. Cancer Res, 67(1): 276-280
|
| 104 |
Palomero T, Barnes K C, Real P J, Glade Bender J L, Sulis M L, Murty V V, Colovai A I, Balbin M, Ferrando A A (2006a). CUTLL1, a novel human T-cell lymphoma cell line with t(7;9) rearrangement, aberrant NOTCH1 activation and high sensitivity to gamma-secretase inhibitors. Leukemia, 20(7): 1279-1287
|
| 105 |
Palomero T, Lim W K, Odom D T, Sulis M L, Real P J, Margolin A, Barnes K C, O’Neil J, Neuberg D, Weng A P,Aster J C, Sigaux F, Soulier J, Look A T, Young R A, Califano A, Ferrando AA(2006b). NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Nat Acad Sci U S A, 103(48): 18261-18266
|
| 106 |
Palomero T, Sulis M L, Cortina M, Real P J, Barnes K, Ciofani M, Caparros E, Buteau J, Brown K, Perkins S L, Bhagat G, Agarwal A M, Basso G, Castillo M, Nagase S, Cordon-Cardo C, Parsons R, Zúñiga-Pflücker J C, Dominguez M, Ferrando A A (2007). Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med, 13(10): 1203-1210
|
| 107 |
Pawson T, Linding R (2008). Network medicine. FEBS Lett, 582(8): 1266-1270
|
| 108 |
Perez-Losada J, Balmain A (2003). Stem-cell hierarchy in skin cancer. Nat Rev Cancer, 3(6): 434-443
|
| 109 |
Pieters R, Carroll W L, (2008). Biology and treatment of acute lymphoblastic leukemia. Pediatric Clinics of NA 24: 1-20
|
| 110 |
Pillai S (1999). The chosen few? Positive selection and the generation of naive B lymphocytes. Immunity, 10(5): 493-502
|
| 111 |
Pillai S, Cariappa A (2009). The follicular versus marginal zone B lymphocyte cell fate decision. Nat Rev Immunol, 9(11): 767-777
|
| 112 |
Pillai S, Cariappa A, Moran S T (2004). Positive selection and lineage commitment during peripheral B-lymphocyte development. Immunol Rev, 197(1): 206-218
|
| 113 |
Priatel J J, Teh S J, Dower N A, Stone J C, Teh H S (2002). RasGRP1 transduces low-grade TCR signals which are critical for T cell development, homeostasis, and differentiation. Immunity, 17(5): 617-627
|
| 114 |
Rajalingam K, Schreck R, Rapp U R, Albert S (2007). Ras oncogenes and their downstream targets. Biochim Biophys Acta, 1773(8): 1177-1195
|
| 115 |
Rambaratsingh R A, Stone J C, Blumberg P M, Lorenzo P S (2003). RasGRP1 represents a novel non-protein kinase C phorbol ester signaling pathway in mouse epidermal keratinocytes. J Biol Chem, 278(52): 52792-52801
|
| 116 |
Ratushny V, Gober M D, Hick R, Ridky T W, Seykora J T (2012). From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. J Clin Invest, 122(2): 464-472
|
| 117 |
Reuther G W, Lambert Q T, Rebhun J F, Caligiuri M A, Quilliam L A, Der C J (2002). RasGRP4 is a novel Ras activator isolated from acute myeloid leukemia. J Biol Chem, 277(34): 30508-30514
|
| 118 |
Roberts D M, Anderson A L, Hidaka M, Swetenburg R L, Patterson C, Stanford W L, Bautch V L (2004). A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters. Mol Cell Biol, 24(24): 10515-10528
|
| 119 |
Rogers S Y, Bradbury D, Kozlowski R, Russell N H (1994). Evidence for internal autocrine regulation of growth in acute myeloblastic leukemia cells. Exp Hematol, 22(7): 593-598
|
| 120 |
Roose J P, Mollenauer M, Gupta V A, Stone J, Weiss A (2005). A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol Cell Biol, 25(11): 4426-4441
|
| 121 |
Roose J P, Mollenauer M, Ho M, Kurosaki T, Weiss A (2007). Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes. Mol Cell Biol, 27(7): 2732-2745
|
| 122 |
Ruiz S, Santos E, Bustelo X R (2007). RasGRF2, a guanosine nucleotide exchange factor for Ras GTPases, participates in T-cell signaling responses. Mol Cell Biol, 27(23): 8127-8142
|
| 123 |
Sharma A, Luke C T, Dower N A, Stone J C, Lorenzo P S (2010). RasGRP1 is essential for ras activation by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in epidermal keratinocytes. J Biol Chem, 285(21): 15724-15730
|
| 124 |
Silva A, Laranjeira A B A, Martins L R, Cardoso B A, Demengeot J, Yunes J A, Seddon B, Barata J T (2011). IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias. Cancer Res, 71(14): 4780-4789
|
| 125 |
Smith-Garvin J E, Koretzky G A, Jordan M S (2009). T cell activation. Annu Rev Immunol, 27(1): 591-619
|
| 126 |
Stang S L, Lopez-Campistrous A, Song X, Dower N A, Blumberg P M, Wender P A, Stone J C (2009). A proapoptotic signaling pathway involving RasGRP, Erk, and Bim in B cells. Exp Hematol, 37(1): 122-134, 134.e2
|
| 127 |
Starr T K, Jameson S C, Hogquist K A (2003). Positive and negative selection of T cells. Annu Rev Immunol, 21(1): 139-176
|
| 128 |
Stolla M, Stefanini L, André P, Ouellette T D, Reilly M P, McKenzie S E, Bergmeier W (2011). CalDAG-GEFI deficiency protects mice in a novel model of Fcγ RIIA-mediated thrombosis and thrombocytopenia. Blood, 118(4): 1113-1120
|
| 129 |
Stone J C (2011). Regulation and Function of the RasGRP Family of Ras Activators in Blood Cells. Genes &. Cancer, 2: 320-334
|
| 130 |
Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian Z R, Du J, Davis A, Mongare M M, Gould J, Frederick D T, Cooper Z A, Chapman P B, Solit D B, Ribas A, Lo R S, Flaherty K T, Ogino S, Wargo J A, Golub T R (2012). Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature, 487(7408): 500-504
|
| 131 |
Su T T, Guo B, Wei B, Braun J, Rawlings D J (2004). Signaling in transitional type 2 B cells is critical for peripheral B-cell development. Immunol Rev, 197(1): 161-178
|
| 132 |
Subramaniam P S, Whye D W, Efimenko E, Chen J, Tosello V, De Keersmaecker K, Kashishian A, Thompson M A, Castillo M, Cordon-Cardo C, Davé U P, Ferrando A, Lannutti B J, Diacovo T G (2012). Targeting nonclassical oncogenes for therapy in T-ALL. Cancer Cell, 21(4): 459-472
|
| 133 |
Suire S, Lécureuil C, Anderson K E, Damoulakis G, Niewczas I, Davidson K, Guillou H, Pan D, Clark J, Hawkins P T, Stephens L (2012). GPCR activation of Ras and PI3Kγ in neutrophils depends on PLCβ2/β3 and the RasGEF RasGRP4. EMBO J, 31(14): 3118-3129
|
| 134 |
Suzuki T, Shen H, Akagi K, Morse H C, Malley J D, Naiman D Q, Jenkins N A, Copeland N G (2002). New genes involved in cancer identified by retroviral tagging. Nat Genet, 32(1): 166-174
|
| 135 |
Tazmini G, Beaulieu N, Woo A, Zahedi B, Goulding R E, Kay R J (2009). Membrane localization of RasGRP1 is controlled by an EF-hand, and by the GEF domain. Biochim Biophys Acta, 1793(3): 447-461
|
| 136 |
Teixeira C, Stang S L, Zheng Y, Beswick N S, Stone J C (2003). Integration of DAG signaling systems mediated by PKC-dependent phosphorylation of RasGRP3. Blood, 102(4): 1414-1420
|
| 137 |
Torres R M, Flaswinkel H, Reth M, Rajewsky K (1996). Aberrant B cell development and immune response in mice with a compromised BCR complex. Science, 272(5269): 1804-1808
|
| 138 |
Townsend S E, Weintraub B C, Goodnow C C (1999). Growing up on the streets: why B-cell development differs from T-cell development. Immunol Today, 20(5): 217-220
|
| 139 |
Vassiliou G S, Cooper J L, Rad R, Li J, Rice S, Uren A, Rad L, Ellis P, Andrews R, Banerjee R, Grove C, Wang W, Liu P, Wright P, Arends M, Bradley A (2011). Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat Genet, 43(5): 470-475
|
| 140 |
Vetter I R, Wittinghofer A (2001). The guanine nucleotide-binding switch in three dimensions. Science, 294(5545): 1299-1304
|
| 141 |
Vigil D, Cherfils J, Rossman K L, Der C J (2010). Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer, 10(12): 842-857
|
| 142 |
Vogelstein B, Papadopoulos N, Velculescu V E, Zhou S, Diaz L A Jr, Kinzler K W (2013). Cancer genome landscapes. Science, 339(6127): 1546-1558
|
| 143 |
von Lintig F C, Huvar I, Law P, Diccianni M B, Yu A L, Boss G R (2000). Ras activation in normal white blood cells and childhood acute lymphoblastic leukemia. Clin Cancer Res, 6(5): 1804-1810
|
| 144 |
Wada H, Masuda K, Satoh R, Kakugawa K, Ikawa T, Katsura Y, Kawamoto H (2008). Adult T-cell progenitors retain myeloid potential. Nature, 452(7188): 768-772
|
| 145 |
Ward A F, Braun B S, Shannon K M (2012). Targeting oncogenic Ras signaling in hematologic malignancies. Blood, 120(17): 3397-3406
|
| 146 |
Watanabe-Okochi N, Oki T, Komeno Y, Kato N, Yuji K, Ono R, Harada Y, Harada H, Hayashi Y, Nakajima H, Nosaka T, Kitaura J, Kitamura T (2009). Possible involvement of RasGRP4 in leukemogenesis. Int J Hematol, 89(4): 470-481
|
| 147 |
Weng A P, Ferrando A A, Lee W, Morris J P 4th, Silverman L B, Sanchez-Irizarry C, Blacklow S C, Look A T, Aster J C (2004). Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science, 306(5694): 269-271
|
| 148 |
Weng A P, Millholland J M, Yashiro-Ohtani Y, Arcangeli M L, Lau A, Wai C, Del Bianco C, Rodriguez C G, Sai H, Tobias J, Li Y, Wolfe M S, Shachaf C, Felsher D, Blacklow S C, Pear W S,
|
| 149 |
Wilson T R, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin D P, Koeppen H, Merchant M, Neve R, Settleman J (2012). Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature, 487(7408): 505-509
|
| 150 |
Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S, Asou N, Kuriyama K, Yagasaki F, Shimazaki C, Akiyama H, Saito K, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Saito H, Ueda R, Ohno R, Naoe T (2001). Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood, 97(8): 2434-2439
|
| 151 |
Yamashita S, Mochizuki N, Ohba Y, Tobiume M, Okada Y, Sawa H, Nagashima K, Matsuda M (2000). CalDAG-GEFIII activation of Ras, R-ras, and Rap1. J Biol Chem, 275(33): 25488-25493
|
| 152 |
Yang D, Kedei N, Li L, Tao J, Velasquez J F, Michalowski A M, Tóth B I, Marincsák R, Varga A, Bíró T, Yuspa S H, Blumberg P M (2010). RasGRP3 contributes to formation and maintenance of the prostate cancer phenotype. Cancer Res, 70(20): 7905-7917
|
| 153 |
Yang D, Tao J, Li L, Kedei N, Tóth Z E, Czap A, Velasquez J F, Mihova D, Michalowski A M, Yuspa S H, Blumberg P M (2011). RasGRP3, a Ras activator, contributes to signaling and the tumorigenic phenotype in human melanoma. 30: 4590-4600
|
| 154 |
Yang Y, Li L, Wong G W, Krilis S A, Madhusudhan M S, Sali A, Stevens R L (2002). RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function. J Biol Chem, 277(28): 25756-25774
|
| 155 |
Yasuda T, Kometani K, Takahashi N, Imai Y, Aiba Y, Kurosaki T (2011). ERKs induce expression of the transcriptional repressor Blimp-1 and subsequent plasma cell differentiation. Sci Signal, 4(169): ra25
|
| 156 |
Yasuda T, Kurosaki T (2008). Regulation of lymphocyte fate by Ras/ERK signals. Cell Cycle, 7(23): 3634-3640
|
| 157 |
Yasuda T, Sanjo H, Pagès G, Kawano Y, Karasuyama H, Pouysségur J, Ogata M, Kurosaki T (2008). Erk kinases link pre-B cell receptor signaling to transcriptional events required for early B cell expansion. Immunity, 28(4): 499-508
|
| 158 |
Yokota S, Nakao M, Horiike S, Seriu T, Iwai T, Kaneko H, Azuma H, Oka T, Takeda T, Watanabe A, Kikuta A, Asami K, Sekine I, Matsushita T, Tsuhciya T, Mimaya J, Koizumi S, Miyake M, Nishikawa K, Takaue Y, Kawano Y, Iwai A, Ishida Y, Matsumoto K, Fujimoto T (1998). Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases. Int J Hematol, 67(4): 379-387
|
| 159 |
Young D C, Griffin J D (1986). Autocrine secretion of GM-CSF in acute myeloblastic leukemia. Blood, 68(5): 1178-1181
|
| 160 |
Zahedi B, Goo H J, Beaulieu N, Tazmini G, Kay R J, Cornell R B (2011). Phosphoinositide 3-kinase regulates plasma membrane targeting of the Ras-specific exchange factor RasGRP1. J Biol Chem, 286(14): 12712-12723
|
| 161 |
Zenatti P P, Ribeiro D, Li W, Zuurbier L, Silva M C, Paganin M, Tritapoe J, Hixon J A, Silveira A B, Cardoso B A, Sarmento L M, Correia N, Toribio M L, Kobarg J, Horstmann M, Pieters R, Brandalise S R, Ferrando A A, Meijerink J P, Durum S K, Yunes J A, Barata J T (2011). Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nat Genet, 43(10): 932-939
|
| 162 |
Zhang J, Ding L, Holmfeldt L, Wu G, Heatley S L, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen S C, Wei L, Collins-Underwood J R, Ma J, Roberts K G, Pounds S B, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki R W, Parker M, McGoldrick D J, Zhao D, Alford D, Espy S, Bobba K C, Song G, Pei D, Cheng C, Roberts S, Barbato M I, Campana D, Coustan-Smith E, Shurtleff S A, Raimondi S C, Kleppe M, Cools J, Shimano K A, Hermiston M L, Doulatov S, Eppert K, Laurenti E, Notta F, Dick J E, Basso G, Hunger S P, Loh M L, Devidas M, Wood B, Winter S, Dunsmore K P, Fulton R S, Fulton L L, Hong X, Harris C C, Dooling D J, Ochoa K, Johnson K J, Obenauer J C, Evans W E, Pui C H, Naeve C W, Ley T J, Mardis E R, Wilson R K, Downing J R, Mullighan C G (2012). The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature, 481(7380): 157-163
|
| 163 |
Zheng Y, Liu H, Coughlin J, Zheng J, Li L, Stone J C (2005). Phosphorylation of RasGRP3 on threonine 133 provides a mechanistic link between PKC and Ras signaling systems in B cells. Blood, 105(9): 3648-3654
|
| 164 |
Zhu M, Fuller D M, Zhang W (2012). The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development. J Biol Chem, 287(11): 8135-8143
|
| 165 |
Zikherman J, Parameswaran R, Weiss A (2012). Endogenous antigen tunes the responsiveness of naive B cells but not T cells. Nature, 489(7414): 160-164
|
/
| 〈 |
|
〉 |