Document Detail


GIT1 is a scaffold for ERK1/2 activation in focal adhesions.
MedLine Citation:
PMID:  15923189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
GIT1 (G protein-coupled receptor kinase-interacting protein 1) has been shown to regulate focal adhesion disassembly. We previously reported that GIT1 associates with MEK1 and acts as a scaffold to enhance ERK1/2 activation. Here, we show that GIT1 co-localizes with ERK1/2 in focal adhesions and regulates cell migration in vascular smooth muscle cells, HEK293 cells, and HeLa cells. Immunofluorescence showed that GIT1 co-localized with phospho-ERK1/2 in focal adhesions after epidermal growth factor stimulation. Because Src is required for both GIT1 tyrosine phosphorylation and focal adhesion disassembly, we studied the effects of Src on GIT1-ERK1/2 interactions. PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) inhibited association of GIT1 with ERK1/2, and their co-localization in focal adhesions was dramatically decreased in SYF-/- cells. GIT1 small interfering RNA significantly inhibited ERK1/2 recruitment to and activation in focal adhesions. GIT1 small interfering RNA and mutated GIT1 lacking the MEK1 binding domain significantly decreased epidermal growth factor-stimulated cell spreading and migration, suggesting that GIT1-mediated events such as ERK1/2 activation are required for spreading and migration. In summary, the present study further supports a key role for GIT1 (a MEK1-binding protein) as a scaffold for signal transduction in focal adhesions.
Authors:
Guoyong Yin; Qinlei Zheng; Chen Yan; Bradford C Berk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-05-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-25     Completed Date:  2005-09-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27705-12     Citation Subset:  IM    
Affiliation:
Center for Cardiovascular Research and Department of Medicine, University of Rochester, Rochester, New York 14642, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing
Animals
Cell Cycle Proteins / metabolism,  physiology*
Cell Line
Cell Movement
Chemotaxis
Cytoskeleton / metabolism
Enzyme Activation
Epidermal Growth Factor / metabolism
Focal Adhesions / metabolism
GTPase-Activating Proteins
Hela Cells
Humans
Immunoblotting
Immunoprecipitation
Mice
Microscopy, Fluorescence
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Mutation
Phosphoproteins / metabolism,  physiology*
Phosphorylation
Plasmids / metabolism
Protein Binding
Protein Structure, Tertiary
RNA Interference
RNA, Small Interfering / metabolism
Signal Transduction
Subcellular Fractions / metabolism
Time Factors
Transfection
Tyrosine / metabolism
src-Family Kinases / metabolism
Grant Support
ID/Acronym/Agency:
R01 HL63462/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Cell Cycle Proteins; 0/GIT1 protein, human; 0/GTPase-Activating Proteins; 0/Git1 protein, mouse; 0/Phosphoproteins; 0/RNA, Small Interfering; 55520-40-6/Tyrosine; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.2/src-Family Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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