|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
17
|
|
pubmed:dateCreated |
1999-7-19
|
|
pubmed:abstractText |
Previous studies by our lab and others established that co-crosslinking sIg and IgG receptor FcgammaRIIb in B cells in a feedback suppression model (negative signaling) promoted tyrosine phosphorylation of the inositol 5-phosphatase SHIP and its interaction with Shc and that these events were associated with inhibition of the Ras pathway. We therefore hypothesized a competition model in which the SH2 domain of SHIP competes with that of Grb2 for binding to phospho-Shc to inhibit the Ras pathway. Here, we provide evidence consistent with this hypothesis. First, FcgammaRIIb-deficient B cells, which do not undergo SHIP tyrosine phosphorylation nor interaction with Shc, displayed an active Ras pathway under negative signaling conditions; reconstitution of FcgammaRIIb expression restored the block in Ras. Second, under conditions of negative signaling leading to SHIP-Shc interaction in wild-type B cells, we observed a profound reduction in the activation-induced association of Grb2 to Sos. Experiments reported here and elsewhere revealed the Grb2-Sos interaction required the engagement of the Grb2 SH2 domain by phospho-Shc. Third, we demonstrated that phospho-Shc cannot concomitantly bind Grb2 and SHIP, indicating that the two proteins competed for the same phospho-tyrosine residue on Shc. These data are consistent with the proposed competition model, and further indicate that the activation induced Grb2-Sos association is rate limiting for Ras activation.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Fc gamma receptor IIB,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/INPPL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgG,
http://linkedlifedata.com/resource/pubmed/chemical/Son of Sevenless Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0161-5890
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
35
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1135-46
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:10395202-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10395202-Animals,
pubmed-meshheading:10395202-Antigens, CD,
pubmed-meshheading:10395202-B-Lymphocytes,
pubmed-meshheading:10395202-GRB2 Adaptor Protein,
pubmed-meshheading:10395202-Membrane Proteins,
pubmed-meshheading:10395202-Mice,
pubmed-meshheading:10395202-Models, Immunological,
pubmed-meshheading:10395202-Phosphoric Monoester Hydrolases,
pubmed-meshheading:10395202-Protein Binding,
pubmed-meshheading:10395202-Proteins,
pubmed-meshheading:10395202-Receptors, IgG,
pubmed-meshheading:10395202-Signal Transduction,
pubmed-meshheading:10395202-Son of Sevenless Proteins,
pubmed-meshheading:10395202-ras Proteins,
pubmed-meshheading:10395202-src Homology Domains
|
|
pubmed:year |
1998
|
|
pubmed:articleTitle |
Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells.
|
|
pubmed:affiliation |
Ohio State University, Department of Microbiology and the Comprehensive Cancer Center, Columbus 43210, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
