Serine phosphorylation regulates paxillin turnover during cell migration

被引：20

作者：

Zeid N.A. ^{[1
]}

Vallés A.-M. ^{[1
]}

Boyer B. ^{[2
]}

机构：

[1] Institut Curie, CNRS UMR146, Centre Universitaire, Orsay

[2] Lab. de Génétique Moléculaire du Développement INSERM UR784, Département de Biologie, Ecole Normale Supérieure, 75005 Paris

来源：

Cell Communication and Signaling | / 4卷 / 1期

关键词：

Focal Adhesion Kinase; Focal Adhesion; Cell Spreading; Paxillin; Serine Phosphorylation;

D O I：

10.1186/1478-811X-4-8

中图分类号：

学科分类号：

摘要：

Background: Paxillin acts as an adaptor protein that localizes to focal adhesion. This protein is regulated during cell migration by phosphorylation on tyrosine, serine and threonine residues. Most of these phosphorylations have been implicated in the regulation of different steps of cell migration. The two major phosphorylation sites of paxillin in response to adhesion to an extracellular matrix are serines 188 and 190. However, the function of this phosphorylation event remains unknown. The purpose of this work was to determine the role of paxillin phosphorylation on residues S188 and S190 in the regulation of cell migration. Results: We used NBT-II epithelial cells that can be induced to migrate when plated on collagen. To examine the role of paxillin serines 188/190 in cell migration, we constructed an EGFP-tagged paxillin mutant in which S188/S190 were mutated into unphosphorylatable alanine residues. We provide evidence that paxillin is regulated by proteasomal degradation following polyubiquitylation of the protein. During active cell migration on collagen, paxillin is protected from proteasome-dependent degradation. We demonstrate that phosphorylation of serines 188/190 is necessary for the protective effect of collagen. In an effort to understand the physiological relevance of paxillin protection from degradation, we show that cells expressing the paxillin S188/190A interfering mutant spread less, have reduced protrusive activity but migrate more actively. Conclusion: Our data demonstrate for the first time that serine-regulated degradation of paxillin plays a key role in the modulation of membrane dynamics and consequently, in the control of cell motility. © 2006 Abou Zeid et al; licensee BioMed Central Ltd.

引用

共 48 条

[1]

Lauffenburger D.A., Horwitz A.F., Cell migration: A physically integrated molecular process, Cell, 84, 3, pp. 359-369, (1996)

[2]

Yamada K.M., Pankov R., Cukierman E., Dimensions and dynamics in integrin function, Braz J Med Biol Res, 36, 8, pp. 959-966, (2003)

[3]

Carragher N.O., Frame M.C., Focal adhesion and actin dynamics: A place where kinases and proteases meet to promote invasion, Trends Cell Biol, 14, 5, pp. 241-249, (2004)

[4]

Laukaitis C.M., Webb D.J., Donais K., Horwitz A.F., Differential dynamics of alpha 5 integrin, paxillin, and alpha-actinin during formation and disassembly of adhesions in migrating cells, J Cell Biol, 153, 7, pp. 1427-1440, (2001)

[5]

Zaidel-Bar R., Ballestrem C., Kam Z., Geiger B., Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells, J Cell Sci, 116, PART 22, pp. 4605-4613, (2003)

[6]

Beckerle M.C., Burridge K., DeMartino G.N., Croall D.E., Colocalization of calcium-dependent protease II and one of its substrates at sites of cell adhesion, Cell, 51, 4, pp. 569-577, (1987)

[7]

Cooray P., Yuan Y., Schoenwaelder S.M., Mitchell C.A., Salem H.H., Jackson S.P., Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain, Biochem J, 318, PART 1, pp. 41-47, (1996)

[8]

Dourdin N., Bhatt A.K., Dutt P., Greer P.A., Arthur J.S., Elce J.S., Huttenlocher A., Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts, J Biol Chem, 276, 51, pp. 48382-48388, (2001)

[9]

Franco S., Perrin B., Huttenlocher A., Isoform specific function of calpain 2 in regulating membrane protrusion, Exp Cell Res, 299, 1, pp. 179-187, (2004)

[10]

Yamaguchi R., Maki M., Hatanaka M., Sabe H., Unphosphorylated and tyrosine-phosphorylated forms of a focal adhesion protein, paxillin, are substrates for calpain II in vitro: Implications for the possible involvement of calpain II in mitosis-specific degradation of paxillin, FEBS Lett, 356, 1, pp. 114-116, (1994)

← 1 2 3 4 5 →