QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online November 5, 2008

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?

A spreading role for PAK and ERK

Upon integrin engagement with the extracellular matrix, the Rho GTPases Cdc42 and Rac promote cell spreading and lamellipodium formation. The serine/threonine kinase PAK1, an effector of Cdc42 and Rac, has been implicated in the regulation of cell spreading – but which of the many potential targets of PAK1 is involved in this process? To address this question, Anne Ridley and colleagues (p. 3729) compare wild-type mouse macrophages with those derived from PAK1-null mice (which exhibit immune defects). The authors first show that PAK1^–/– macrophages have enhanced cell spreading, but reduced lamellipodial stability. In normal macrophages, the chemoattractant CSF1 transiently stimulates the activation of MAP kinases such as ERK1/2; by contrast, ERK1/2 activation is reduced in CSF1-treated PAK1^–/– macrophages, although chemotaxis is unaffected. During adhesion, too, ERK1/2 activity is decreased in the absence of PAK1 – particularly at the cell periphery, where lamellipodia form. Notably, inhibition of ERK1/2 in wild-type macrophages promotes lamellipodial instability and cell spreading. Thus, the authors conclude that PAK1 regulates lamellipodial dynamics through the activation of ERK1/2. Their results shed light on the Rho GTPase-dependent pathways that control cell motility and adhesion.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

PAK1-mediated activation of ERK1/2 regulates lamellipodial dynamics

Stephen D. Smith, Zahara M. Jaffer, Jonathan Chernoff, and Anne J. Ridley
JCS 2008 121: 3729-3736. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?