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Phosphorylation of ADF/cofilins


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).


Signal transduction pathways and  the cofilin kinases


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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