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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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