Document Detail

SHP-1 regulates Fcgamma receptor-mediated phagocytosis and the activation of RAC.
MedLine Citation:
PMID:  12176909     Owner:  NLM     Status:  MEDLINE    
Fcgamma receptor-mediated phagocytosis is a complex process involving the activation of protein tyrosine kinases, events that are potentially down-regulated by protein tyrosine phosphatases. We used the J774A.1 macrophage cell line to examine the roles played by the protein tyrosine phosphatase SHP-1 in the negative regulation of Fcgamma receptor-mediated phagocytosis. Stimulation with sensitized sheep red blood cells (sRBCs) induced tyrosine phosphorylation of CBL and association of CBL with CRKL. These events were completely or partially abrogated by PP1 or the heterologous expression of dominant-negative SYK, respectively. Heterologous expression of wild-type but not catalytically inactive SHP-1 also completely abrogated the phagocytosis of IgG-sensitized sRBCs. Most notably, overexpressed SHP-1 associates with CBL and this association led to CBL dephosphorylation, loss of the CBL-CRKL interaction, and the suppression of Rac activation. These data represent the first direct evidence that SHP-1 is involved in the regulation of Fcgamma receptor-mediated phagocytosis and suggest that activating signals mediated by SRC family kinases SYK, CBL, phosphatidyl inositol-3 (PI-3) kinase, and Rac are directly opposed by inhibitory signals through SHP-1.
Anita M Kant; Pradip De; Xiaodong Peng; Taolin Yi; David J Rawlings; Jong Suk Kim; Donald L Durden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  100     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-14     Completed Date:  2002-09-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1852-9     Citation Subset:  AIM; IM    
Herman B. Wells Center for Pediatrics Research, Indiana University School of Medicine, Indianapolis 46202, USA.
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MeSH Terms
Cell Line
Gene Expression Regulation / physiology
Intracellular Signaling Peptides and Proteins
Macrophages / physiology
Phagocytosis / physiology*
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / physiology*
Receptors, IgG / physiology*
Signal Transduction
rac GTP-Binding Proteins / antagonists & inhibitors,  physiology*
src Homology Domains / physiology
Grant Support
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Receptors, IgG; EC Tyrosine Phosphatase, Non-Receptor Type 6; EC Tyrosine Phosphatases; EC protein, mouse; EC GTP-Binding Proteins

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