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PMID: 17485491 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

alpha v beta3 and alpha5beta1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration.

The Journal of cell biology ·Vol. 177 ·No. 3 ·2007-05-07 ·Pages 515-25

White DP, Caswell PT, Norman JC

Abstract

Accumulating evidence suggests that integrin recycling regulates cell migration. However, the lack of reagents to selectively target the trafficking of individual heterodimers, as opposed to endocytic transport as a whole, has made it difficult to define the contribution made by particular recycling pathways to directional cell movement. We show that autophosphorylation of protein kinase D1 (PKD1) at Ser(916) is necessary for its association with alphavbeta3 integrin. Expression of PKD1(916A) or the use of mutants of beta3 that do not bind to PKD1 selectively inhibits short-loop, Rab4-dependent recycling of alphavbeta3, and this suppresses the persistence of fibroblast migration. However, we report that short-loop recycling does not directly contribute to fibroblast migration by moving alphavbeta3 to the cell front, but by antagonizing alpha5beta1 recycling, which, in turn, influences the cell's decision to migrate with persistence or to move randomly.

MeSH Terms

Animals COS Cells Cell Movement/genetics Chlorocebus aethiops Endocytosis/genetics Fibroblasts/cytology,metabolism Gene Expression Integrin alpha5beta1/genetics,metabolism Integrin alphaVbeta3/genetics,metabolism Intracellular Signaling Peptides and Proteins/genetics,metabolism Mice Mutation, Missense NIH 3T3 Cells Phosphorylation Protein Binding/genetics Protein Kinase C/genetics,metabolism Protein Serine-Threonine Kinases/genetics,metabolism Protein Transport/genetics Signal Transduction/genetics rab4 GTP-Binding Proteins/genetics,metabolism rho-Associated Kinases

Chemicals

Integrin alpha5beta1 Integrin alphaVbeta3 Intracellular Signaling Peptides and Proteins protein kinase D Protein Serine-Threonine Kinases rho-Associated Kinases Protein Kinase C rab4 GTP-Binding Proteins

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

White Dominic P

Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Bearsden, Glasgow, Scotland, UK.

Caswell Patrick T

Norman Jim C

References (32)

32 references, click to expand

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Article Info

Journal

The Journal of cell biology

Abbr.

J Cell Biol

ISSN

0021-9525

DOI

10.1083/jcb.200609004

Published

2007-05-07

Pages

515-25

Language

English

Region

United States

NLM ID

0375356

PMCID

PMC2064808

Subset

Grants

Wellcome Trust · United Kingdom

External Links

PubMed source DOI: 10.1083/jcb.200609004 PMC Full Text View journal details

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alpha v beta3 and alpha5beta1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration.

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