Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases

被引：58

作者：

Lee, Chan-Soo ^{[1
,2
]}

Choi, Chang-Ki ^{[1
,2
]}

Shin, Eun-Young ^{[1
,2
]}

Schwartz, Martin Alexander ^{[3
,4
,5
]}

Kim, Eung-Gook ^{[1
,2
]}

机构：

[1] Chungbuk Natl Univ, Coll Med, Dept Biochem, Cheongju 361763, South Korea

[2] Chungbuk Natl Univ, Coll Med, Med Res Ctr, Cheongju 361763, South Korea

[3] Univ Virginia, Mellon Prostate Canc Res Ctr, Robert M Berne Cardiovasc Res, Dept Microbiol, Charlottesville, VA 22908 USA

[4] Univ Virginia, Mellon Prostate Canc Res Ctr, Robert M Berne Cardiovasc Res, Dept Cell Biol, Charlottesville, VA 22908 USA

[5] Univ Virginia, Mellon Prostate Canc Res Ctr, Robert M Berne Cardiovasc Res, Dept Biomed Engn, Charlottesville, VA 22908 USA

来源：

JOURNAL OF CELL BIOLOGY | 2010年 / 190卷 / 04期

关键词：

CELL-MIGRATION; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; ADHESION DYNAMICS; SMOOTH-MUSCLE; ALPHA-ACTININ; KINASE; PHOSPHORYLATION; MOTILITY; RAC;

D O I：

10.1083/jcb.201003057

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cell migration requires the coordinated spatiotemporal regulation of actomyosin contraction and cell protrusion/adhesion. Nonmuscle myosin II (MII) controls Rac1 and Cdc42 activation, and cell protrusion and focal complex formation in migrating cells. However, these mechanisms are poorly understood. Here, we show that MII interacts specifically with multiple Dbl family guanine nucleotide exchange factors (GEFs). Binding is mediated by the conserved tandem Dbl homology-pleckstrin homology module, the catalytic site of these GEFs, with dissociation constants of similar to 0.3 mu M. Binding to the GEFs required assembly of the MII into filaments and actin-stimulated ATPase activity. Binding of MII suppressed GEF activity. Accordingly, inhibition of MII ATPase activity caused release of GEFs and activation of Rho GTPases. Depletion of beta PIX GEF in migrating NIH3T3 fibroblasts suppressed lamellipodial protrusions and focal complex formation induced by MII inhibition. The results elucidate a functional link between MII and Rac1/Cdc42 GTPases, which may regulate protrusion/adhesion dynamics in migrating cells.

引用

页码：663 / 674

页数：12