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PMID: 16537926 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Glycogen synthase kinase 3- and extracellular signal-regulated kinase-dependent phosphorylation of paxillin regulates cytoskeletal rearrangement.

Molecular and cellular biology ·Vol. 26 ·No. 7 ·2006-04-00 ·Pages 2857-68

Cai X, Li M, Vrana J, Schaller MD

Abstract

Paxillin is a 68-kDa focal adhesion-associated protein that plays an important role in controlling cell spreading and migration. Phosphorylation of paxillin regulates its biological activity and thus has warranted investigation. Serine 126 and serine 130 were previously identified as two major extracellular signal-regulated kinase (ERK)-dependent phosphorylation sites in Raf-transformed fibroblasts. Here serine 126 is identified as a phosphorylation site induced by lipopolysaccharide (LPS) stimulation of RAW264.7 cells. A number of other stimuli, including adhesion and colony-stimulating factor, induce serine 126 phosphorylation in RAW264.7 cells, and nerve growth factor (NGF) treatment induces serine 126 phosphorylation in PC12 cells. The kinase responsible for phosphorylation of this site is identified as glycogen synthase kinase 3 (GSK-3). Interestingly, this GSK-3-dependent phosphorylation is regulated via an ERK-dependent priming mechanism, i.e., phosphorylation of serine 130. Phosphorylation of S126/S130 was required to promote spreading in paxillin null cells, and LPS-induced spreading of RAW264.7 cells was inhibited by expression of the paxillin S126A/S130A mutant. Furthermore, this mutant also retarded NGF-induced PC12 cell neurite outgrowth. Hence, phosphorylation of paxillin on serines 126 and 130, which is mediated by an ERK/GSK-3 dual-kinase mechanism, plays an important role in cytoskeletal rearrangement.

MeSH Terms
Animals Cell Movement Cytoskeleton/metabolism Extracellular Signal-Regulated MAP Kinases/metabolism Fibroblasts/cytology Glycogen Synthase Kinase 3/antagonists & inhibitors,metabolism Humans Lipopolysaccharides/pharmacology Macrophages/cytology,drug effects Mice Nerve Growth Factors/pharmacology Neurites/drug effects PC12 Cells Paxillin/metabolism Phosphorylation/drug effects Protein Transport Rats Serine/metabolism Tyrosine/metabolism
Chemicals
Lipopolysaccharides Nerve Growth Factors Paxillin Tyrosine Serine Extracellular Signal-Regulated MAP Kinases Glycogen Synthase Kinase 3
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cai Xinming
Department of Cell and Developmental Biology, 534 Taylor Hall, CB # 7090, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Li Min
Vrana Julie
Schaller Michael D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.7.2857-2868.2006
Published
2006-04-00
Pages
2857-68
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1430314
Subset
IM
Grants
NHLBI NIH HHS · P01 HL045100 · United States
NCI NIH HHS · R01 CA090901 · United States
NCI NIH HHS · CA90901 · United States
NHLBI NIH HHS · HL45100 · United States
External Links
PubMed source DOI: 10.1128/MCB.26.7.2857-2868.2006 PMC Full Text View journal details
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