REVIEW

Regulation of phagocytosis by TAM receptors and their ligands

  • Qingxian LU , 1,2 ,
  • Qiutang LI 1 ,
  • Qingjun LU 2,3
Expand
  • 1. Departments of Ophthalmology and Visual Sciences, Anatomical Sciences and Neurobiology; Kentucky Lions Eye Center and James Brown Cancer Center; University of Louisville School of Medicine; 301 E. Muhammad Ali Blvd. Louisville, KY40202, USA
  • 2. Beijing School of Ophthalmology, Capital Medical University, Beijing 100069, China
  • 3. Beijing Institute of Ophthalmology, Tong Ren Eye Center, Beijing 100730, China

Received date: 01 Feb 2010

Accepted date: 19 Mar 2010

Published date: 01 Jun 2010

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

The TAM family of receptors is preferentially expressed by professional and non-professional phagocytes, including macrophages, dendritic cells and natural killer cells in the immune system, osteoclasts in bone, Sertoli cells in testis, and retinal pigmental epithelium cells in the retina. Mutations in the Mertk single gene or in different combinations of the double or triple gene mutations in the same cell cause complete or partial impairment in phagocytosis of their preys; and as a result, either the normal apoptotic cells cannot be efficiently removed or the tissue neighbor cells die by apoptosis. This scenario of TAM regulation represents a widely adapted model system used by phagocytes in all different tissues. The present review will summarize current known functional roles of TAM receptors and their ligands, Gas 6 and protein S, in the regulation of phagocytosis.

Cite this article

Qingxian LU , Qiutang LI , Qingjun LU . Regulation of phagocytosis by TAM receptors and their ligands[J]. Frontiers in Biology, 2010 , 5(3) : 227 -237 . DOI: 10.1007/s11515-010-0034-5

Acknowledgement

This study was partially supported by NIH EY018830, RR017702, and RR018733 and Research to Prevent Blindness; and the National Natural Science Foundation of China (Grant Nos. 30400229, 30670643 and 30870788).
1
Ait-Oufella H, Pouresmail V, Simon T, Blanc-Brude O, Kinugawa K, Merval R, Offenstadt G, Lesèche G, Cohen P L, Tedgui A, Mallat Z (2008). Defective mer receptor tyrosine kinase signaling in bone marrow cells promotes apoptotic cell accumulation and accelerates atherosclerosis. Arterioscler Thromb Vasc Biol, 28(8): 1429-1431

DOI

2
Anderson H A, Maylock C A, Williams J A, Paweletz C P, Shu H, Shacter E (2003). Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol, 4(1): 87-91

DOI

3
Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F, Arnout J, Dewerchin M, Hoylaerts M, Herbert J, Collen D, Dahlbäck B, Carmeliet P (2001). Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med, 7(2): 215-221

DOI

4
Araki N, Johnson M T, Swanson J A (1996). A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol, 135(5): 1249-1260

DOI

5
Bellosta P, Zhang Q, Goff S P, Basilico C (1997). Signaling through the ARK tyrosine kinase receptor protects from apoptosis in the absence of growth stimulation. Oncogene, 15(20): 2387-2397

DOI

6
Bernstein P S, Law W C, Rando R R (1987). Biochemical characterization of the retinoid isomerase system of the eye. J Biol Chem, 262(35): 16848-16857

7
Bok D, Hall M O (1971). The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the rat. J Cell Biol, 49(3): 664-682

DOI

8
Braunger J, Schleithoff L, Schulz A S, Kessler H, Lammers R, Ullrich A, Bartram C R, Janssen J W (1997). Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene, 14(22): 2619-2631

DOI

9
Burstyn-Cohen T, Heeb MJ, Lemke G (2009). Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis. J Clin Invest, 119(10): 2942-2953

DOI

10
Camenisch T D, Koller B H, Earp H S, Matsushima G K (1999). A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and lipopolysaccharide-induced endotoxic shock. J Immunol, 162(6): 3498-3503

11
Caraux A, Lu Q, Fernandez N, Riou S, Di Santo J P, Raulet D H, Lemke G, Roth C (2006). Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases. Nat Immunol, 7(7): 747-754

DOI

12
Charbel Issa P, Bolz H J, Ebermann I, Domeier E, Holz F G, Scholl H P (2009). Characterisation of severe rod-cone dystrophy in a consanguineous family with a splice site mutation in the MERTK gene. Br J Ophthalmol, 93(7): 920-925

DOI

13
Chen J, Carey K, Godowski P J (1997). Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation. Oncogene, 14(17): 2033-2039

DOI

14
D’Angelo A, Viganò D’Angelo S (2008). Protein S deficiency. Haematologica, 93(4): 498-501

DOI

15
D’Cruz P M, Yasumura D, Weir J, Matthes M T, Abderrahim H, LaVail M M, Vollrath D (2000). Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet, 9(4): 645-651

DOI

16
Dahlbäck B (1991). Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system. Thromb Haemost, 66(1): 49-61

17
Dowling J E, Sidman R L (1962). Inherited retinal dystrophy in the rat. J Cell Biol, 14: 73-109

DOI

18
Duncan J L, LaVail M M, Yasumura D, Matthes M T, Yang H, Trautmann N, Chappelow A V, Feng W, Earp H S, Matsushima G K, Vollrath D (2003a). An RCS-like retinal dystrophy phenotype in mer knockout mice. Invest Ophthalmol Vis Sci, 44(2): 826-838

DOI

19
Duncan J L, Yang H, Vollrath D, Yasumura D, Matthes M T, Trautmann N, Chappelow A V, Feng W, Earp H S, Matsushima G K, LaVail M M (2003b). Inherited retinal dystrophy in Mer knockout mice. Adv Exp Med Biol, 533: 165-172

20
Edwards R B, Szamier R B (1977). Defective phagocytosis of isolated rod outer segments by RCS rat retinal pigment epithelium in culture. Science, 197(4307): 1001-1003

DOI

21
Feng W, Yasumura D, Matthes M T, LaVail M M, Vollrath D (2002). Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells. J Biol Chem, 277(19): 17016-17022

DOI

22
Finnemann S C (2003). Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J, 22(16): 4143-4154

DOI

23
Finnemann S C, Rodriguez-Boulan E (1999). Macrophage and retinal pigment epithelium phagocytosis: apoptotic cells and photoreceptors compete for alphavbeta3 and alphavbeta5 integrins, and protein kinase C regulates alphavbeta5 binding and cytoskeletal linkage. J Exp Med, 190(6): 861-874

DOI

24
Gal A, Li Y, Thompson D A, Weir J, Orth U, Jacobson S G, Apfelstedt-Sylla E, Vollrath D (2000). Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet, 26(3): 270-271

DOI

25
García de Frutos P, Fuentes-Prior P, Hurtado B, Sala N (2007). Molecular basis of protein S deficiency. Thromb Haemost, 98(3): 543-556

26
Georgescu M M, Kirsch K H, Shishido T, Zong C, Hanafusa H (1999). Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NF-kappaB. Mol Cell Biol, 19(2): 1171-1181

27
Godowski P J, Mark M R, Chen J, Sadick M D, Raab H, Hammonds R G (1995). Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3. Cell, 82(3): 355-358

DOI

28
Graham D K, Dawson T L, Mullaney D L, Snodgrass H R, Earp H S (1994). Cloning and mRNA expression analysis of a novel human protooncogene, c-mer. Cell Growth Differ, 5(6): 647-657

29
Hafizi S, Dahlbäck B (2006). Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev, 17(4): 295-304

DOI

30
Hall M O, Abrams T (1987). Kinetic studies of rod outer segment binding and ingestion by cultured rat RPE cells. Exp Eye Res, 45(6): 907-922

DOI

33
Hall M O, Agnew B J, Abrams T A, Burgess B L (2003). The phagocytosis of os is mediated by the PI3-kinase linked tyrosine kinase receptor, mer, and is stimulated by GAS6. Adv Exp Med Biol, 533: 331-336

34
Hall M O, Obin M S, Heeb M J, Burgess B L, Abrams T A (2005). Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat retinal pigment epithelial cells. Exp Eye Res, 81(5): 581-591

DOI

32
Hall M O, Obin M S, Prieto A L, Burgess B L, Abrams T A (2002). Gas6 binding to photoreceptor outer segments requires gamma-carboxyglutamic acid (Gla) and Ca(2+) and is required for OS phagocytosis by RPE cells in vitro. Exp Eye Res, 75(4): 391-400

DOI

31
Hall M O, Prieto A L, Obin M S, Abrams T A, Burgess B L, Heeb M J, Agnew B J (2001). Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6. Exp Eye Res, 73(4): 509-520

DOI

35
Hasanbasic I, Rajotte I, Blostein M (2005). The role of gamma-carboxylation in the anti-apoptotic function of gas6. J Thromb Haemost, 3(12): 2790-2797

DOI

36
Huang M, Rigby A C, Morelli X, Grant M A, Huang G, Furie B, Seaton B, Furie B C (2003). Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins. Nat Struct Biol, 10(9): 751-756

DOI

38
Hubbard S R, Mohammadi M, Schlessinger J (1998). Autoregulatory mechanisms in protein-tyrosine kinases. J Biol Chem, 273(20): 11987-11990

DOI

37
Hubbard S R, Till J H (2000). Protein tyrosine kinase structure and function. Annu Rev Biochem, 69: 373-398

DOI

39
Ishimoto Y, Ohashi K, Mizuno K, Nakano T (2000). Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J Biochem, 127(3): 411-417

40
Janssen J W, Schulz A S, Steenvoorden A C, Schmidberger M, Strehl S, Ambros P F, Bartram C R (1991). A novel putative tyrosine kinase receptor with oncogenic potential. Oncogene, 6(11): 2113-2120

41
Jia R, Hanafusa H (1994). The proto-oncogene of v-eyk (v-ryk) is a novel receptor-type protein tyrosine kinase with extracellular Ig/GN-III domains. J Biol Chem, 269(3): 1839-1844

42
Kamen L A, Levinsohn J, Swanson J A (2007). Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes. Mol Biol Cell. 8(7): 2463-2472

DOI

43
Keating A K, Salzberg D B, Sather S, Liang X, Nickoloff S, Anwar A, Deryckere D, Hill K, Joung D, Sawczyn K K, Park J, Curran-Everett D, McGavran L, Meltesen L, Gore L, Johnson G L, Graham D K (2006). Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase. Oncogene, 25(45): 6092-6100

DOI

44
Lai C, Gore M, Lemke G (1994). Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase. Oncogene, 9(9): 2567-2578

45
LaVail M M (1973). Kinetics of rod outer segment renewal in the developing mouse retina. J Cell Biol, 58(3): 650-661

DOI

46
LaVail M M (1976). Rod outer segment disk shedding in rat retina: relationship to cyclic lighting. Science, 194(4269): 1071-1074

DOI

47
Lemke G, Lu Q (2003). Macrophage regulation by Tyro 3 family receptors. Curr Opin Immunol, 15(1): 31-36

DOI

48
Lemke G, Rothlin C V (2008). Immunobiology of the TAM receptors. Nat Rev Immunol, 8(5): 327-336

DOI

50
Lu Q, Gore M, Zhang Q, Camenisch T, Boast S, Casagranda F, Lai C, Skinner M K, Klein R, Matsushima G K, Earp H S, Goff S P, Lemke G (1999). Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature, 398(6729): 723-728

DOI

49
Lu Q, Lemke G (2001). Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science, 293(5528): 306-311

DOI

51
Lundwall A, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlbäck B, Stenflo J, Wydro R (1986). Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc Natl Acad Sci U S A, 83(18): 6716-6720

DOI

52
Maeda Y, Shiratsuchi A, Namiki M, Nakanishi Y (2002). Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility. Cell Death Differ, 9(7): 742-749

DOI

53
Maguire A M, Simonelli F, Pierce E A, Pugh E N Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall K A, Testa F, Surace E M, Rossi S, Lyubarsky A, Arruda V R, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma J X, Redmond T M, Zhu X, Hauck B, Zelenaia O, Shindler K S, Maguire M G, Wright J F, Volpe N J, McDonnell J W, Auricchio A, High K A, Bennett J (2008). Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med, 358(21): 2240-2248

DOI

54
Mahajan N P, Earp H S (2003). An SH2 domain-dependent, phosphotyrosine-independent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing guanine nucleotide-exchange factor action. J Biol Chem, 278(43): 42596-42603

DOI

55
Manfioletti G, Brancolini C, Avanzi G, Schneider C (1993). The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol, 13(8): 4976-4985

56
Manning G, Whyte D B, Martinez R, Hunter T, Sudarsanam S (2002). The protein kinase complement of the human genome. Science, 298(5600): 1912-1934

DOI

57
Mark M R, Chen J, Hammonds R G, Sadick M, Godowsk P J (1996). Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl. J Biol Chem, 271(16): 9785-9789

DOI

58
May R C, Machesky L M (2001). Phagocytosis and the actin cytoskeleton. J Cell Sci, 114(Pt 6): 1061-1077

59
Mayerson P L, Hall M O (1986). Rat retinal pigment epithelial cells show specificity of phagocytosis in vitro. J Cell Biol, 103(1): 299-308

DOI

60
Mays R W, Beck K A, Nelson W J (1994). Organization and function of the cytoskeleton in polarized epithelial cells: a component of the protein sorting machinery. Curr Opin Cell Biol, 6(1): 16-24

DOI

61
McHenry C L, Liu Y, Feng W, Nair A R, Feathers K L, Ding X, Gal A, Vollrath D, Sieving P A, Thompson D A (2004). MERTK arginine-844-cysteine in a patient with severe rod-cone dystrophy: loss of mutant protein function in transfected cells. Invest Ophthalmol Vis Sci, 45(5): 1456-1463

DOI

62
Miething A (1992). Germ-cell death during prespermatogenesis in the testis of the golden hamster. Cell Tissue Res, 267(3): 583-590

DOI

63
Miljanich G P, Nemes P P, White D L, Dratz E A (1981). The asymmetric transmembrane distribution of phosphatidylethanolamine, phosphatidylserine, and fatty acids of the bovine retinal rod outer segment disk membrane. J Membr Biol, 60(3): 249-255

DOI

64
Mullen R J, LaVail M M (1976). Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras. Science, 192(4241): 799-801

DOI

65
Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (1996). Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem, 271(47): 30022-30027

DOI

67
Nakano T, Ishimoto Y, Kishino J, Umeda M, Inoue K, Nagata K, Ohashi K, Mizuno K, Arita H (1997). Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6. J Biol Chem, 272(47): 29411-29414

DOI

66
Nakano T, Kawamoto K, Kishino J, Nomura K, Higashino K, Arita H (1997). Requirement of gamma-carboxyglutamic acid residues for the biological activity of Gas6: contribution of endogenous Gas6 to the proliferation of vascular smooth muscle cells. Biochem J, 323(Pt 2): 387-392

68
Nandrot E, Dufour E M, Provost A C, Péquignot M O, Bonnel S, Gogat K, Marchant D, Rouillac C, Sépulchre de Condé B, Bihoreau M T, Shaver C, Dufier J L, Marsac C, Lathrop M, Menasche M, Abitbol M M (2000). Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis. Neurobiol Dis, 7(6 Pt B): 586-599

DOI

70
Nandrot E F, Anand M, Sircar M, Finnemann S C (2006). Novel role for alphavbeta5-integrin in retinal adhesion and its diurnal peak. Am J Physiol Cell Physiol, 290(4): C1256-C1262

DOI

69
Nandrot E F, Kim Y, Brodie S E, Huang X, Sheppard D, Finnemann S C (2004). Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin. J Exp Med, 200(12): 1539-1545

DOI

71
Niedergang F, Chavrier P (2004). Signaling and membrane dynamics during phagocytosis: many roads lead to the phagos(R)ome. Curr Opin Cell Biol, 16(4): 422-428

DOI

72
O’Bryan J P, Frye R A, Cogswell P C, Neubauer A, Kitch B, Prokop C, Espinosa R 3rd, Le Beau M M, Earp H S, Liu E T (1991). axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol Cell Biol, 11(10): 5016-5031

73
Ohashi K, Mizuno K, Kuma K, Miyata T, Nakamura T (1994). Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain. Oncogene, 9(3): 699-705

74
Prasad D, Rothlin C V, Burrola P, Burstyn-Cohen T, Lu Q, Garcia de Frutos P, Lemke G (2006). TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci, 33(1): 96-108

DOI

75
Rescigno J, Mansukhani A, Basilico C (1991). A putative receptor tyrosine kinase with unique structural topology. Oncogene, 6(10): 1909-1913

76
Robinson D R, Wu Y M, Lin S F (2000). The protein tyrosine kinase family of the human genome. Oncogene, 19(49): 5548-5557

DOI

77
Rothlin C V, Ghosh S, Zuniga E I, Oldstone M B, Lemke G (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell, 131(6): 1124-1136

DOI

78
Saller F, Brisset A C, Tchaikovski S N, Azevedo M, Chrast R, Fernández J A, Schapira M, Hackeng T M, Griffin J H, Angelillo-Scherrer A (2009). Generation and phenotypic analysis of protein S-deficient mice. Blood, 114(11): 2307-2314

DOI

79
Sasaki T, Knyazev P G, Cheburkin Y, Göhring W, Tisi D, Ullrich A, Timpl R, Hohenester E (2002). Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains. J Biol Chem, 277(46): 44164-44170

DOI

80
Sasaki T, Knyazev P G, Clout N J, Cheburkin Y, Göhring W, Ullrich A, Timpl R, Hohenester E (2006). Structural basis for Gas6-Axl signalling. EMBO J, 25(1): 80-87

DOI

81
Sather S, Kenyon K D, Lefkowitz J B, Liang X, Varnum B C, Henson P M, Graham D K (2007). A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood, 109(3): 1026-1033

DOI

82
Schlessinger J (2000). Cell signaling by receptor tyrosine kinases. Cell, 103(2): 211-225

DOI

83
Schneider C, King R M, Philipson L (1988). Genes specifically expressed at growth arrest of mammalian cells. Cell, 54(6): 787-793

DOI

84
Scott R S, McMahon E J, Pop S M, Reap E A, Caricchio R, Cohen P L, Earp H S, Matsushima G K (2001). Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature, 411(6834): 207-211

DOI

85
Seitz H M, Camenisch T D, Lemke G, Earp H S, Matsushima G K (2007). Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol, 178(9): 5635-5642

86
Sen P, Wallet M A, Yi Z, Huang Y, Henderson M, Mathews C E, Earp H S, Matsushima G, Baldwin A S Jr, Tisch R M (2007). Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood, 109(2): 653-660

DOI

87
Shankar S L, O’Guin K, Cammer M, McMorris F A, Stitt T N, Basch R S, Varnum B, Shafit-Zagardo B (2003). The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway. J Neurosci, 23(10): 4208-4218

88
Shankar S L, O’Guin K, Kim M, Varnum B, Lemke G, Brosnan C F, Shafit-Zagardo B (2006). Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis. J Neurosci, 26(21): 5638-5648

DOI

89
Smith A J, Schlichtenbrede F C, Tschernutter M, Bainbridge J W, Thrasher A J, Ali R R (2003). AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa. Mol Ther, 8(2): 188-195

DOI

90
Songyang Z, Shoelson S E, Chaudhuri M, Gish G, Pawson T, Haser W G, King F, Roberts T, Ratnofsky S, Lechleider R J, (1993). SH2 domains recognize specific phosphopeptide sequences. Cell, 72(5): 767-778

DOI

91
Stitt T N, Conn G, Gore M, Lai C, Bruno J, Radziejewski C, Mattsson K, Fisher J, Gies D R, Jones P F, (1995). The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell, 80(4): 661-670

DOI

92
Sugo T, Dahlbäck B, Holmgren A, Stenflo J (1986). Calcium binding of bovine protein S. Effect of thrombin cleavage and removal of the gamma-carboxyglutamic acid-containing region. J Biol Chem, 261(11): 5116-5120

93
Swanson J A, Johnson M T, Beningo K, Post P, Mooseker M, Araki N (1999). A contractile activity that closes phagosomes in macrophages. J Cell Sci, 112(Pt 3): 307-316

94
Taylor P R, Carugati A, Fadok V A, Cook H T, Andrews M, Carroll M C, Savill J S, Henson P M, Botto M, Walport M J (2000). A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med, 192(3): 359-366

DOI

95
Thorp E, Cui D, Schrijvers D M, Kuriakose G, Tabas I (2008). Mertk receptor mutation reduces efferocytosis efficiency and promotes apoptotic cell accumulation and plaque necrosis in atherosclerotic lesions of apoe-/- mice. Arterioscler Thromb Vasc Biol, 28(8): 1421-1428

DOI

96
Thorp E, Li Y, Bao L, Yao P M, Kuriakose G, Rong J, Fisher E A, Tabas I (2009). Brief report: increased apoptosis in advanced atherosclerotic lesions of Apoe-/- mice lacking macrophage Bcl-2. Arterioscler Thromb Vasc Biol, 29(2): 169-172

DOI

97
Tibrewal N, Wu Y, D’mello V, Akakura R, George T C, Varnum B, Birge R B (2008). Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation. J Biol Chem, 283(6): 3618-3627

DOI

98
Todt J C, Hu B, Curtis J L (2004). The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages. J Leukoc Biol, 75(4): 705-713

DOI

100
Tschernutter M, Jenkins S A, Waseem N H, Saihan Z, Holder G E, Bird A C, Bhattacharya S S, Ali R R, Webster A R (2006). Clinical characterisation of a family with retinal dystrophy caused by mutation in the Mertk gene. Br J Ophthalmol, 90(6): 718-723

DOI

99
Tschernutter M, Schlichtenbrede F C, Howe S, Balaggan K S, Munro P M, Bainbridge J W, Thrasher A J, Smith A J, Ali R R (2005). Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther, 12(8): 694-701

DOI

101
Vollrath D, Feng W, Duncan J L, Yasumura D, D’Cruz P M, Chappelow A, Matthes M T, Kay M A, LaVail M M (2001). Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci U S A, 98(22): 12584-12589

DOI

102
Wang H, Wang H, Xiong W, Chen Y, Ma Q, Ma J, Ge Y, Han D (2006). Evaluation on the phagocytosis of apoptotic spermatogenic cells by Sertoli cells in vitro through detecting lipid droplet formation by Oil Red O staining. Reproduction, 132(3): 485-492

DOI

103
Williams J C, Craven R R, Earp H S, Kawula T H, Matsushima G K (2009). TAM receptors are dispensable in the phagocytosis and killing of bacteria. Cell Immunol, 259(2): 128-134

DOI

104
Wu Y, Singh S, Georgescu M M, Birge R B (2005). A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci, 118(Pt 3): 539-553

DOI

105
Xiong W, Chen Y, Wang H, Wang H, Wu H, Lu Q, Han D (2008). Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction, 135(1): 77-87

DOI

106
Young R W (1967). The renewal of photoreceptor cell outer segments. J Cell Biol, 33(1): 61-72

DOI

107
Young R W, Bok D (1969). Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol, 42(2): 392-403

DOI

108
Zheng Y, Zhang L, Lu Q, Wang X, Yu F, Wang X, Lu Q (2009). NGF-induced Tyro3 and Axl function as survival factors for differentiating PC12 cells. Biochem Biophys Res Commun, 378(3): 371-375

DOI

Outlines

/