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Protein Kinase C 

Page updated 19/6/02

Many different isoforms of protein kinase C (PKC) exist in cells and they are central to many signal transduction mechanisms.  There are three classes of PKC; the conventional PKCs are associated with and activated by anionic phospholipids.  The conventional PKC members are : PKCa, PKCbI and bII, PKCg.  Novel PKCs include : PKCd, PKCe, PKCh and PKCq.  Atypical PKCs include :  PKCl/i and PKCz. Many PKCs are also actin-binding proteins (Blobe et al, 1996; Nakhost et al, 1998; Prekeris et al, 1998; Slater et al, 2000; Lopez-Lluch et al, 2001), the first description of actin binding (I think), was PKCz (Gomez et al, 1995).  In some isoforms a particular actin binding motif has been identified (LKKQET), this motif is similar to regions of other actin binding proteins (Table 1) that are known to bind actin through it and this peptide competes with PKC for binding to actin (Prekeris et al, 1998).

Protein Sequence  Region Reference
PKC LKKQET  Prekeris et al, 1998
PKCd C2 -like domain Lopez-Lluch et al, 2001

Thymosin b4

LKEAET

LKETET

Actobindin LKHAET
Villin (head)
Table 1  Shared Actin binding motifs

The significance of PKC binding to actin and their mutual regulation may be understandable in the context of the exocytosis of chromaffin cells.  In these cells activation of PKC by phorbol esters induces the disassembly of the cortical actin cytoskeleton and increased exocytosis (Vitale et al, 1992).

Protein Kinase C phosphorylates Actin Binding Proteins.

Protein that PKC phosphorylate are many and varied and include many actin binding proteins so that activation of PKC in cells may lead to altered actin cytoskeleton by means other than direct effects of PKC itself (Table 2). 

Actin-binding Protein Substrate Sites Effect on actin binding References
 
Adducin Matsuoka et al, 1996
Calponin S175
Dematin No effect on actin binding Husain-Chishti et al, 1988 & 1989
EGF receptor
Fascin S39 human Reduces actin binding & bundling Yamakita et al, 1996; Ono et al, 1997
MARKS
Myosin light chains
Table 2  The effect of PKC phosphorylation

References:-

Blobe, G.C., Stribling, D.S., Fabbro, D., Stabel, S., Hannun, Y.A., (1996). "Protein kinase C bII specifically binds to and is activated by F-actin.". J.Biol.Chem. 271, 15823-15830.

Gomez, J., Martinez de Aragon, A., Bonay, P., Pitton, A., Garcia, A., Silva, M., Fresno, M., Alvarez, A. & Rebello, A. (1995). "Physical association and functional relationship between protein kinase C zeta and the cytoskeleton." Eur.J.Immunol. 25, 2673-2678.

Husain-Chishti, A., Faquin, W., Wu, C.-C. & Brandon, D. (1989). J.Biol.Chem. 264, 8985-8991.

Husain-Chishti, A. et al, (1988). Nature 334, 718-721.

Lopez-Lluch, G., Bird, M. M., Canas, B., Godovac-Zimmerman, J., Ridley, A., Segal, A. W. & Dekker, L. V. (2001) Protein kinase C-d C2-like domain is a binding site for actin and enables actin redistribution in neutrophils., Biochem. J. 357, 39-47.

Matsuoka, Y., Hughes, C.A., & Bennett, V. (1996). "" J.Biol.Chem. 271, 25157-25166.

Nakhost, A., Forscher, P. & Sossin, W. (1998) "Binding of protein kinase C isoforms to actin in Aplysia." J. Neurochem. 71, 1221-1231.

Ono, S., Yamakita, Y., Yamashiro, S., Matsudaira, P.T. , Gnarra, J.R., Obinata, T. & Matsumura, F. (1997). J.Biol.Chem. 272, 2527-2533.

Prekeris, R., Hernandez, R.M., Mayhew, M.W., White, M.K. & Terrian, D.M. (1998). "Molecular analysis of the interaction between protein kinase C-e and filamentous actin.". J.Biol.Chem. 273, 26790-26798.

Slater, S. J., Milano, S. K., Stagliano, B. A., Gergich, K. J., Curry, J. P., Taddeo, F. J. & Stubbs, C. D. (2000) "Interaction of protein kinase C with filamentous actin: Isozyme specificity resulting from divergent phorbol ester and calcium dependencies." Biochemistry. 39, 271-280.

Slater, S. J., Stafliano, B. A., Seiz, J. L., Curry, J. P., Milano, S. K., Gergich, K. J. & Stubbs, C. D. (2001) "Effects of ethanol on protein kinase C activity induced by filamentous actin." Biochim.Biophys.Acta. 1544, 207-216.

Vitale, M.L., Rodriguez Del Castillo, A., Trifaro, J.M., (1992). "Protein kinase C activation by phorbol esters induces chromaffin cell cortical filamentous actin disassembly and increases the initial rate of exocytosis in response to nicotinic receptor stimulation." Neuroscience 51, 463-474.

Yamakita, Y., Ono, S., Matsumura, F. & Yamashiro, S. (1996). J.Biol.Chem. 271, 12632-12638.

Zeidman, R., Troller, U., Ragunath, A., Pahlman, S. & Larsson, C. (2002) Protein kinase Ce actin-binding site is important for neurite outgrowth during neuronal differentiation., Mol.Biol. Cell. 13, 12-24.

 
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