Document Detail

Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells.
MedLine Citation:
PMID:  12972546     Owner:  NLM     Status:  MEDLINE    
Platelet endothelial adhesion molecule-1 (PECAM-1) is a part of intercellular junctions and triggers intracellular signaling cascades upon homophilic binding. The intracellular domain of PECAM-1 is tyrosine phosphorylated upon homophilic engagement. However, it remains unclear which tyrosine kinase phosphorylates PECAM-1. We sought to isolate tyrosine kinases responsible for PECAM-1 phosphorylation and identified Fer as a candidate, based on expression cloning. Fer kinase specifically phosphorylated PECAM-1 at the immunoreceptor tyrosine-based inhibitory motif. Notably, Fer induced tyrosine phosphorylation of SHP-2, which is known to bind to the immunoreceptor tyrosine-based inhibitory motif of PECAM-1, and Fer also induced tyrosine phosphorylation of Gab1 (Grb2-associated binder-1). Engagement-dependent PECAM-1 phosphorylation was inhibited by the overexpression of a kinase-inactive mutant of Fer, suggesting that Fer is responsible for the tyrosine phosphorylation upon PECAM-1 engagement. Furthermore, by using green fluorescent protein-tagged Fer and a time-lapse fluorescent microscope, we found that Fer localized at microtubules in polarized and motile vascular endothelial cells. Fer was dynamically associated with growing microtubules in the direction of cell-cell contacts, where p120catenin, which is known to associate with Fer, colocalized with PECAM-1. These results suggest that Fer localized on microtubules may play an important role in phosphorylation of PECAM-1, possibly through its association with p120catenin at nascent cell-cell contacts.
Naoko Kogata; Michitaka Masuda; Yuji Kamioka; Akiko Yamagishi; Akira Endo; Masato Okada; Naoki Mochizuki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-06-13
Journal Detail:
Title:  Molecular biology of the cell     Volume:  14     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-15     Completed Date:  2004-04-08     Revised Date:  2010-01-29    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3553-64     Citation Subset:  IM    
Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
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MeSH Terms
Adaptor Proteins, Signal Transducing
Antigens, CD31 / metabolism*,  physiology
Cell Adhesion / physiology
Cell Adhesion Molecules / metabolism,  physiology
Cells, Cultured
Cloning, Molecular
Endothelial Cells / enzymology*,  physiology
Gene Library
Green Fluorescent Proteins
Intracellular Signaling Peptides and Proteins
Luminescent Proteins
Microtubules / enzymology*,  metabolism,  physiology
Phosphoproteins / metabolism*,  physiology
Protein Structure, Tertiary
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases / metabolism,  physiology
Protein-Tyrosine Kinases
Proto-Oncogene Proteins / metabolism*,  physiology
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD31; 0/Cell Adhesion Molecules; 0/GAB1 protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/Luminescent Proteins; 0/Phosphoproteins; 0/Proto-Oncogene Proteins; 0/delta catenin; 110736-90-8/proto-oncogene protein c-fes-fps; 147336-22-9/Green Fluorescent Proteins; EC Kinases; EC protein, human; EC Tyrosine Phosphatase, Non-Receptor Type 11; EC Tyrosine Phosphatases

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