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ADF/Cofilin binding proteins

The number one AC binding protein is of course actin, but cofilin binds several other proteins partners including the expected regulatory kinases and phosphatases (table 1), and less expected partners such as membrane channels and the AIP1 actin-binding protein.


Protein Function References
AIP-1 Not clear at present but binds actin and co-operates with AC to depolymerize actin. Amberg et al, 1995; Okada et al, 1999; Rodal et al, 1999
CAP Cyclase Associated Protein (Asp65). Another actin-binding protein. CAP also activates and Adenylate Cyclase.  CAP binds and modulates the activity of cofilin also. Moriyama & Yahara 2002
Cofilin Cofilin has been reported to bind itself, the significance of this observation is contentious as cofilins are rich in cysteine Pfannstiel et al, 2001
LIM kinase 1 Phosphorylates AC on the conserved ser3 (or equivalent).  Cofilin is presently the only known substrate for this kinase. Arber et al, 1998;Yang et al, 1998
LIM kinase 2 A second isoform of LM kinase which also phosphorylates ACs. Sumi et al, 1999
TESK 1 A widely expressed kinase that phosphorylates AC. Has homology to the LIM kinases. Toshima et al, 2000 & 2001a
TESK 2 Another widely expressed kinase suntype  that phosphorylates AC. Toshima et al, 2001b
Na,K-ATPase a subunit A channel that exchanges intracellular sodium for extracellular potassium. Lee et al, 2001
Neutrophil Kinase An unidentified kinase from neutrophils that is able to phosphorylate ser3 of cofilin Lian et al, 2000
PP1 & PP2A Serine phosphatases, removes ser3 phosphate from vertebrate cofilins Ambach et al, 2000
Slingshot An F-actin binding protein that is also a phosphatase for the ACs Niwa et al, 2002
Table 1  ADF/cofilin binding proteins

Ambach, A., Saunus, J., Konstandin, M., Wesselborg, S., Meuer, S. C. & Samsag, Y. (2000) The serine phosphatases PP1 and PP2A associate with and activate the actin-binding protein cofilin in human T lymphocytes. Eur. J. Immunol. 30, 3422-3431.

Amberg, D. C., Basart, E. & Botstein, D. (1995) Defining protein interactions with yeast actin in vivo. Nature Struct. Biol. 2, 28-35.

Arber, S., Barbayannis, F. A., Hanser, H., Schneider, C., Stanyon, C. A., Bernard, O. & Caroni, P. (1998) Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature. 393, 805-809.

Lee, K., Jung, J., Kim, M. & Guidotti, G. (2001) Interaction of the a subunit of Na, K-ATPase with cofilin. Biochem. J. 353, 377-385.

Lian, J. P., Marks, P. G., Wang, J. Y., Falls, D. L. & Badwey, J. A. (2000) A protein kinase from neutrophils that specifically recognizes Ser-3 in cofilin., J.Biol.Chem. 275, 2869-2876.

Moriyama, K. & Yahara, I. (2002) Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover. J.Cell Sci. 115, 1591-1601.

Niwa, R., Nagata-Ohashi, K., Takeichi, M., Mizuno, K. & Uemura, T. (2002) Control of actin reorganization by slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 108, 233-246.

Okada, K., Obinata, T. & Abe, H. (1999) XAIP1: a Xenopus homoloque of yeast actin interacting protein 1 (AIP1), which induces disassembly of actin filaments cooperatively with ADF/cofilin family proteins. J.Cell Sci. 112, 1553-1565.

Pfannstiel, J., Cyrklaff, M., Habermann, A., Stoeva, S., Griffiths, G., Shoeman, R. & Faulstich, H. (2001) Human cofilin forms oligomers exhibiting actin bundling activity. J. Biol.Chem. 276, 49476-49484.

Rodal, A. A., Tetreault, J. W., Lappalainen, P., Drubin, D. G. & Amberg, D. C. (1999) Aip1p interacts with cofilin to disassemble actin filaments. J.Cell Biol. 145, 1251-1264.

Sumi, T., Matsumoto, K., Takai, Y. & Nakamura, T. (1999) Cofilin phosphorylation and actin cytoskletal dynamics regulated by Rho-and Cdc42-activated LIM-kinase 2. J.Cell Biol. 147, 1519-1532.

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 phospholrylation 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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