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A regulated
form of ADF/cofilin was first observed by and it was
subsequently shown that this modification was phosphorylation (Agnew
et al, 1995).
Phosphorylation of ADF/cofilin on serine 3 (human non-cofilin
equivalent) results in inhibition of actin binding. Cofilin
is only very weakly phosphorylated by PKC (Akiyama
et al,1986),
but efficiently phosphorylated by LIM kinase1 (Yang
et al, 1998)
and LIM kinase2 (), another as yet unidentified kinase from
neutrophils, TESK1 (Toshima
et al, 2000;
Toshma et
al, 2001a)
and TESK2 (Toshima
et al, 2001b)
in animal cells and by a calcium sensitive kinase in plants (Smertenko
et al, 1998)
. To date all the kinases that have been found to
significantly phosphorylate ACs do so at a serine close to the
N-terminus of the protein. This is usually the second
amino-acid but many plants have the equivalent serine more
distant from the N-terminus. Phosphorylation virtually
abolishes the actin binding function of all ACs phosphorylated
but (disappointingly) this does not result in a change in
overall structure (Blanchoin
et al, 2000).
However, in all structures to date regions at the N and C
termini have not been included as their position cannot be rigorously
determined as they are so motile and so it remains possible that
phosphorylation affects actin binding by perturbing the
structure of these parts (most likely the N-terminus).
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References:-
Agnew, B. J., Minamide, L. S. &
Bamburg, J. R. (1995) Reactivation of phosphorylated actin
depolymerizing factor and identification of the regulatory site., J.
Biol. Chem. 270, 17582-17587.
Blanchoin, L., Robinson, R. C., Choe,
S. & Pollard, T. D. (2000) Phosphorylation of Acanthamoeba
actophorin (ADF/cofilin) blocks interaction with actin without a change
in atomic structure., J.Mol.Biol. 295, 203-211.
Smertenko, A. P., Jiang, C.-J.,
Simmons, N. J., Weeds, A. G., Davies, D. R. & Hussey, P. J. (1998)
Ser6 in the maize actin-depolymerizing factor, ZmADF3, is phosphorylated
by a calcium-stimulated protein kinase and is essential for the control
of functional activity., Plant J. 14, 187-193.
Toshima, J., Toshima, J. Y. & Mizuno, K.
(2000) Cofilin phosphorylation by protein kinase TESK1 and its role in
integrin-mediated actin remodeling, Molecular Biology of the Cell. 11,
915.
Toshima, J., Toshima, J. Y., Amano, T., Yang,
N., Narumiya, S. & Mizuno, K. (2001a) Cofilin phosphorylation by
protein kinase testicular protein kinase 1 and its role in integrin-mediated
actin reorganization and focal adhesion formation., Mol. Biol. of the
Cell. 12, 1131-1145.
Toshima, J., Toshima, J. Y., Takeuchi, K.,
Mori, R. & Mizuno, K. (2001b) Cofilin phosphorylation and actin
reorganization activities of testicular protein kinase 2 and its
predominant expression in testicular sertoli cells., J. Biol.Chem.
276, 31449-31458.
Yang, N., Higuchi, O., Ohashi, K.,
Nagata, K., Wada, A., Kangawa, K., Nishida, E. & Mizuno, K. (1998)
Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated
actin reorganization, Nature. 393, 809-812.
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Signal
transduction pathways and the cofilin kinases