Received date: 02 Nov 2010
Accepted date: 29 Nov 2010
Published date: 01 Aug 2011
Copyright
Protein kinase C (PKC) is a family of serine/threonine protein kinases that plays a central role in transducing extracellular signals into a variety of intracellular responses ranging from cell proliferation to apoptosis. Nine PKC genes have been identified in the human genome, which encode 10 proteins. Each member of this protein kinase family displays distinct biochemical characteristics and is enriched in different cellular and subcellular locations. Activation of PKC has been implicated in the regulation of cell growth and differentiation. This review summarizes works of the past years in the field of PKC biochemistry that covers regulation and activation mechanism of different PKC isoforms.
Key words: PKC; biochemistry; PKC kinase; PKC phosphatases; PKC structure
Julhash U. KAZI . The mechanism of protein kinase C regulation[J]. Frontiers in Biology, 2011 , 6(4) : 328 -336 . DOI: 10.1007/s11515-011-1070-5
1 |
Balendran A, Hare G R, Kieloch A, Williams M R, Alessi D R (2000). Further evidence that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is required for the stability and phosphorylation of protein kinase C (PKC) isoforms. FEBS Lett, 484(3): 217-223
|
2 |
Benes C H, Wu N, Elia A E, Dharia T, Cantley L C, Soltoff S P (2005). The C2 domain of PKCdelta is a phosphotyrosine binding domain. Cell, 121(2): 271-280
|
3 |
Berridge M J, Irvine R F (1984). Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature, 312(5992): 315-321
|
4 |
Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982). Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem, 257(13): 7847-7851
|
5 |
Cenni V, Döppler H, Sonnenburg E D, Maraldi N, Newton A C, Toker A (2002). Regulation of novel protein kinase C epsilon by phosphorylation. Biochem J, 363(Pt 3): 537-545
|
6 |
Chou M M, Hou W, Johnson J, Graham L K, Lee M H, Chen C S, Newton A C, Schaffhausen B S, Toker A (1998). Regulation of protein kinase C zeta by PI 3-kinase and PDK-1. Curr Biol, 8(19): 1069-1077
|
7 |
Corbalán-García S, Rodríguez-Alfaro J A, Gómez-Fernández J C (1999). Determination of the calcium-binding sites of the C2 domain of protein kinase Calpha that are critical for its translocation to the plasma membrane. Biochem J, 337(Pt 3): 513-521
|
8 |
Corbalán-Garcia S, Sánchez-Carrillo S, García-García J, Gómez-Fernández J C (2003). Characterization of the membrane binding mode of the C2 domain of PKC epsilon. Biochemistry, 42(40): 11661-11668
|
9 |
Denning M F, Dlugosz A A, Threadgill D W, Magnuson T, Yuspa S H (1996). Activation of the epidermal growth factor receptor signal transduction pathway stimulates tyrosine phosphorylation of protein kinase C delta. J Biol Chem, 271(10): 5325-5331
|
10 |
Döppler H, Storz P (2007). A novel tyrosine phosphorylation site in protein kinase D contributes to oxidative stress-mediated activation. J Biol Chem, 282(44): 31873-31881
|
11 |
Dutil E M, Keranen L M, DePaoli-Roach A A, Newton A C (1994). In vivo regulation of protein kinase C by trans-phosphorylation followed by autophosphorylation. J Biol Chem, 269(47): 29359-29362
|
12 |
Dutil E M, Toker A, Newton A C (1998). Regulation of conventional protein kinase C isozymes by phosphoinositide-dependent kinase 1 (PDK-1). Curr Biol, 8(25): 1366-1375
|
13 |
Edwards A S, Faux M C, Scott J D, Newton A C (1999). Carboxyl-terminal phosphorylation regulates the function and subcellular localization of protein kinase C betaII. J Biol Chem, 274(10): 6461-6468
|
14 |
England K, Watson J, Beale G, Warner M, Cross J, Rumsby M (2001). Signalling pathways regulating the dephosphorylation of Ser729 in the hydrophobic domain of protein kinase Cepsilon upon cell passage. J Biol Chem, 276(13): 10437-10442
|
15 |
Gatti A, Robinson P J (1997). Okadaic acid interferes with phorbol-ester-mediated down-regulation of protein kinase C-alpha, C-delta and C-epsilon. Eur J Biochem, 249: 92-97
|
16 |
Grodsky N, Li Y, Bouzida D, Love R, Jensen J, Nodes B, Nonomiya J, Grant S (2006). Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor. Biochemistry, 45(47): 13970-13981
|
17 |
Gschwendt M, Kielbassa K, Kittstein W, Marks F (1994). Tyrosine phosphorylation and stimulation of protein kinase C delta from porcine spleen by src in vitro. Dependence on the activated state of protein kinase C delta. FEBS Lett, 347(1): 85-89
|
18 |
Guerrero-Valero M, Ferrer-Orta C, Querol-Audí J, Marin-Vicente C, Fita I, Gómez-Fernández J C, Verdaguer N, Corbalán-García S (2009). Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2. Proc Natl Acad Sci U S A, 106(16): 6603-6607
|
19 |
Hansra G, Bornancin F, Whelan R, Hemmings B A, Parker P J (1996). 12-O-Tetradecanoylphorbol-13-acetate-induced dephosphorylation of protein kinase Calpha correlates with the presence of a membrane-associated protein phosphatase 2A heterotrimer. J Biol Chem, 271(51): 32785-32788
|
20 |
Hirano Y, Yoshinaga S, Ogura K, Yokochi M, Noda Y, Sumimoto H, Inagaki F (2004). Solution structure of atypical protein kinase C PB1 domain and its mode of interaction with ZIP/p62 and MEK5. J Biol Chem, 279(30): 31883-31890
|
21 |
Hirano Y, Yoshinaga S, Takeya R, Suzuki N N, Horiuchi M, Kohjima M, Sumimoto H, Inagaki F (2005). Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains. J Biol Chem, 280(10): 9653-9661
|
22 |
House C, Kemp B E (1987). Protein kinase C contains a pseudosubstrate prototope in its regulatory domain. Science, 238: 1726-1728
|
23 |
House C, Kemp B E (1990). Protein kinase C pseudosubstrate prototope: structure-function relationships. Cell Signal, 2(2): 187-190
|
24 |
Joy S V, Scates A C, Bearelly S, Dar M, Taulien C A, Goebel J A, Cooney M J (2005). Ruboxistaurin, a protein kinase C beta inhibitor, as an emerging treatment for diabetes microvascular complications. Ann Pharmacother, 39(10): 1693-1699
|
25 |
Kawakami Y, Kitaura J, Yao L, McHenry R W, Kawakami Y, Newton A C, Kang S, Kato R M, Leitges M, Rawlings D J, Kawakami T (2003). A Ras activation pathway dependent on Syk phosphorylation of protein kinase C. Proc Natl Acad Sci U S A, 100(16): 9470-9475
|
26 |
Kazi J U, Kabir N N, Soh J W (2008). Bioinformatic prediction and analysis of eukaryotic protein kinases in the rat genome. Gene, 410(1): 147-153
|
27 |
Keranen L M, Dutil E M, Newton A C (1995). Protein kinase C is regulated in vivo by three functionally distinct phosphorylations. Curr Biol, 5(12): 1394-1403
|
28 |
Kikkawa U, Takai Y, Tanaka Y, Miyake R, Nishizuka Y (1983). Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters. J Biol Chem, 258(19): 11442-11445
|
29 |
Kitatani K, Idkowiak-Baldys J, Hannun Y A (2007). Mechanism of inhibition of sequestration of protein kinase C alpha/betaII by ceramide. Roles of ceramide-activated protein phosphatases and phosphorylation/dephosphorylation of protein kinase C alpha/betaII on threonine 638/641. J Biol Chem, 282(28): 20647-20656
|
30 |
Koide H, Ogita K, Kikkawa U, Nishizuka Y (1992). Isolation and characterization of the epsilon subspecies of protein kinase C from rat brain. Proc Natl Acad Sci U S A, 89(4): 1149-1153
|
31 |
Konishi H, Yamauchi E, Taniguchi H, Yamamoto T, Matsuzaki H, Takemura Y, Ohmae K, Kikkawa U, Nishizuka Y (2001). Phosphorylation sites of protein kinase C delta in H2O2-treated cells and its activation by tyrosine kinase in vitro. Proc Natl Acad Sci U S A, 98(12): 6587-6592
|
32 |
Le GoodJ.A., , ZieglerW.H., , ParekhD.B., , AlessiD.R., , CohenP., , and ParkerP.J., (1998). Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science, 281: 2042-2045
|
33 |
Leach K L, James M L, Blumberg P M (1983). Characterization of a specific phorbol ester aporeceptor in mouse brain cytosol. Proc Natl Acad Sci U S A, 80(14): 4208-4212
|
34 |
Lee I H, Lim H J, Yoon S, Seong J K, Bae D S, Rhee S G, Bae Y S (2008). Ahnak protein activates PKC through dissociation of PKC-PP2A complex. J Biol Chem, 283: 6312-6320
|
35 |
Lee K Y, D'Acquist F., Hayden M S, Shim J H, Ghosh S (2005). PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation. Science, 308: 114-118
|
36 |
Littler D R, Walker J R, She Y M, Finerty P J Jr, Newman E M, Dhe-Paganon S (2006). Structure of human protein kinase C eta (PKCeta) C2 domain and identification of phosphorylation sites. Biochem Biophys Res Commun, 349(4): 1182-1189
|
37 |
Liu Y, Witte S, Liu Y C, Doyle M, Elly C, Altman A (2000). Regulation of protein kinase Ctheta function during T cell activation by Lck-mediated tyrosine phosphorylation. J Biol Chem, 275(5): 3603-3609
|
38 |
Lo H H, Bartek G A, Fischer S M (1994). In vitro activation of mouse skin protein kinase C by fatty acids and their hydroxylated metabolites. Lipids, 29(8): 547-553
|
39 |
Mackay H J, Twelves C J (2007). Targeting the protein kinase C family: are we there yet? Nat Rev Cancer, 7: 554-562
|
40 |
Makowske M, Rosen O M (1989). Complete activation of protein kinase C by an antipeptide antibody directed against the pseudosubstrate prototope. J Biol Chem, 264(27): 16155-16159
|
41 |
Medkova M, Cho W (1998). Mutagenesis of the C2 domain of protein kinase C-alpha. Differential roles of Ca2+ ligands and membrane binding residues. J Biol Chem, 273(28): 17544-17552
|
42 |
Mellor H, Parker P J (1998). The extended protein kinase C superfamily. Biochem J, 332(Pt 2): 281-292
|
43 |
Messerschmidt A, Macieira S, Velarde M, Bädeker M, Benda C, Jestel A, Brandstetter H, Neuefeind T, Blaesse M (2005). Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif. J Mol Biol, 352(4): 918-931
|
44 |
Moscat J, Diaz-Meco M T, Albert A, Campuzano S (2006). Cell signaling and function organized by PB1 domain interactions. Mol Cell, 23(5): 631-640
|
45 |
Müller G, Ayoub M, Storz P, Rennecke J, Fabbro D, Pfizenmaier K (1995). PKC zeta is a molecular switch in signal transduction of TNF-alpha, bifunctionally regulated by ceramide and arachidonic acid. EMBO J, 14(9): 1961-1969
|
46 |
Murakami K, Chan S Y, Routtenberg A (1986). Protein kinase C activation by cis-fatty acid in the absence of Ca2+ and phospholipids. J Biol Chem, 261(33): 15424-15429
|
47 |
Murakami K, Routtenberg A (1985). Direct activation of purified protein kinase C by unsaturated fatty acids (oleate and arachidonate) in the absence of phospholipids and Ca2+. FEBS Lett, 192(2): 189-193
|
48 |
Newton A C (2001). Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem Rev, 101(8): 2353-2364
|
49 |
Newton A C (2003). Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem J, 370(Pt 2): 361-371
|
50 |
Newton A C, Koshland D E Jr (1987). Protein kinase C autophosphorylates by an intrapeptide reaction. J Biol Chem, 262(21): 10185-10188
|
51 |
Ochoa W F, Garcia-Garcia J, Fita I, Corbalan-Garcia S, Verdaguer N, Gomez-Fernandez J C (2001). Structure of the C2 domain from novel protein kinase Cepsilon. A membrane binding model for Ca(2+)-independent C2 domains. J Mol Biol, 311(4): 837-849
|
52 |
Ogita K, Miyamoto S, Yamaguchi K, Koide H, Fujisawa N, Kikkawa U, Sahara S, Fukami Y, Nishizuka Y (1992). Isolation and characterization of delta-subspecies of protein kinase C from rat brain. Proc Natl Acad Sci U S A, 89(5): 1592-1596
|
53 |
Orr J W, Newton A C (1994). Intrapeptide regulation of protein kinase C. J Biol Chem, 269(11): 8383-8387
|
54 |
Pappa H, Murray-Rust J, Dekker L V, Parker P J, McDonald N Q (1998). Crystal structure of the C2 domain from protein kinase C-delta. Structure, 6(7): 885-894
|
55 |
Parekh D, Ziegler W, Yonezawa K, Hara K, Parker P J (1999). Mammalian TOR controls one of two kinase pathways acting upon nPKCdelta and nPKCepsilon. J Biol Chem, 274(49): 34758-34764
|
56 |
Pike A C W, Amos A, Johansson C, Sobott F, Savitsky P, Berridge G, Fedorov O, Umeano C, Gorrec F, Bunkoczi G,
|
57 |
Rybin V O, Guo J, Gertsberg Z, Elouardighi H, Steinberg S F (2007). Protein kinase Cepsilon (PKCepsilon) and Src control PKCdelta activation loop phosphorylation in cardiomyocytes. J Biol Chem, 282(32): 23631-23638
|
58 |
Rybin V O, Sabri A, Short J, Braz J C, Molkentin J D, Steinberg S F (2003). Cross-regulation of novel protein kinase C (PKC) isoform function in cardiomyocytes. Role of PKC epsilon in activation loop phosphorylations and PKC delta in hydrophobic motif phosphorylations. J Biol Chem, 278(16): 14555-14564
|
59 |
Seibenhener M L, Roehm J, White W O, Neidigh K B, Vandenplas M L, Wooten M W (1999). Identification of Src as a novel atypical protein kinase C-interacting protein. Mol Cell Biol Res Commun, 2(1): 28-31
|
60 |
Shen G X (2003). Selective protein kinase C inhibitors and their applications. Curr Drug Targets Cardiovasc Haematol Disord, 3(4): 301-307
|
61 |
Shinomura T, Asaoka Y, Oka M, Yoshida K, Nishizuka Y (1991). Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications. Proc Natl Acad Sci USA, 88(12): 5149-5153
|
62 |
Sonnenburg E D, Gao T, Newton A C (2001). The phosphoinositide-dependent kinase, PDK-1, phosphorylates conventional protein kinase C isozymes by a mechanism that is independent of phosphoinositide 3-kinase. J Biol Chem, 276(48): 45289-45297
|
63 |
Srivastava J, Goris J, Dilworth S M, Parker P J (2002). Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides. FEBS Lett, 516(1-3): 265-269
|
64 |
Sumimoto H, Kamakura S, Ito T (2007). Structure and function of the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants. Sci STKE, 2007(401): re6
|
65 |
Sun X, Wu F, Datta R, Kharbanda S, Kufe D (2000). Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress. J Biol Chem, 275(11): 7470-7473
|
66 |
Sutton R B, Sprang S R (1998). Structure of the protein kinase Cbeta phospholipid-binding C2 domain complexed with Ca2+. Structure, 6(11): 1395-1405
|
67 |
Szallasi Z, Bogi K, Gohari S, Biro T, Acs P, Blumberg P M (1996). Non-equivalent roles for the first and second zinc fingers of protein kinase Cdelta. Effect of their mutation on phorbol ester-induced translocation in NIH 3T3 cells. J Biol Chem, 271(31): 18299-18301
|
68 |
Szallasi Z, Denning M F, Chang E Y, Rivera J, Yuspa S H, Lehel C, Olah Z, Anderson W B, Blumberg P M (1995). Development of a rapid approach to identification of tyrosine phosphorylation sites: application to PKC delta phosphorylated upon activation of the high affinity receptor for IgE in rat basophilic leukemia cells. Biochem Biophys Res Commun, 214(3): 888-894
|
69 |
Toker A, Meyer M, Reddy K K, Falck J R, Aneja R, Aneja S, Parra A, Burns D J, Ballas L M, Cantley L C (1994). Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3. J Biol Chem, 269(51): 32358-32367
|
70 |
Tominaga M, Kitagawa Y, Tanaka S, Kishimoto A (1991). Phosphorylation of type II (beta) protein kinase C by casein kinase II. J Biochem, 110(4): 655-660
|
71 |
Verdaguer N, Corbalan-Garcia S, Ochoa W F, Fita I, Gómez-Fernández J C (1999). Ca2+ bridges the C2 membrane-binding domain of protein kinase Calpha directly to phosphatidylserine. EMBO J, 18(22): 6329-6338
|
72 |
Vila J, Walker J M, Itarte E, Weber M J, Sando J J (1989). Phosphorylation of protein kinase C by casein kinase-1. FEBS Lett, 255(1): 205-208
|
73 |
Wooten M W, Vandenplas M L, Seibenhener M L, Geetha T, Diaz-Meco M T (2001). Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase C’s via a src kinase pathway. Mol Cell Biol, 21(24): 8414-8427
|
74 |
Xu R X, Pawelczyk T, Xia T H, Brown S C (1997). NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions. Biochemistry, 36(35): 10709-10717
|
75 |
Xu Z B, Chaudhary D, Olland S, Wolfrom S, Czerwinski R, Malakian K, Lin L, Stahl M L, Joseph-McCarthy D, Benander C, Fitz L, Greco R, Somers W S, Mosyak L (2004). Catalytic domain crystal structure of protein kinase C-theta (PKCtheta). J Biol Chem, 279(48): 50401-50409
|
76 |
Zhang G, Kazanietz M G, Blumberg P M, Hurley J H (1995). Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester. Cell, 81(6): 917-924
|
77 |
Ziegler W H, Parekh D B, Le Good J A, Whelan R D, Kelly J J, Frech M, Hemmings B A, Parker P J (1999). Rapamycin-sensitive phosphorylation of PKC on a carboxy-terminal site by an atypical PKC complex. Curr Biol, 9(10): 522-529
|
/
〈 | 〉 |