Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-4-13
pubmed:abstractText
Inhibitory receptors on hemopoietic cells critically regulate cellular function. Despite their expression on a variety of cell types, these inhibitory receptors signal through a common mechanism involving tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM), which engages Src homology 2 (SH2) domain-containing cytoplasmic tyrosine or inositol phosphatases. In this study, we have investigated the proximal signal-transduction pathway of an ITIM-bearing receptor, gp49B, a member of a newly described family of murine NK and mast cell receptors. We demonstrate that the tyrosine residues within the ITIMs are phosphorylated and serve for the association and activation of the cytoplasmic tyrosine phosphatase SHP-1. Furthermore, we demonstrate a physiologic association between gp49B and SHP-1 by coimmunoprecipitation studies from NK cells. To address the mechanism of binding between gp49B and SHP-1, binding studies involving glutathione S-transferase SHP-1 mutants were performed. Utilizing the tandem SH2 domains of SHP-1, we show that either SH2 domain can interact with phosphorylated gp49B. Full-length SHP-1, with an inactivated amino SH2 domain, also retained gp49B binding. However, binding to gp49B was disrupted by inactivation of the carboxyl SH2 domain of full-length SHP-1, suggesting that in the presence of the phosphatase domain, the carboxyl SH2 domain is required for the recruitment of phosphorylated gp49B. Thus, gp49B signaling involves SHP-1, and this association is dependent on tyrosine phosphorylation of the gp49B ITIMs, and an intact SHP-1 carboxyl SH2 domain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface, http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers, http://linkedlifedata.com/resource/pubmed/chemical/Gp49a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Lilrb4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PTPN6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/SH2 Domain-Containing Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1318-23
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9973385-Amino Acid Sequence, pubmed-meshheading:9973385-Animals, pubmed-meshheading:9973385-Antigens, Surface, pubmed-meshheading:9973385-B-Lymphocytes, pubmed-meshheading:9973385-Base Sequence, pubmed-meshheading:9973385-Binding Sites, pubmed-meshheading:9973385-Cell Line, pubmed-meshheading:9973385-DNA Primers, pubmed-meshheading:9973385-Humans, pubmed-meshheading:9973385-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:9973385-Jurkat Cells, pubmed-meshheading:9973385-Killer Cells, Natural, pubmed-meshheading:9973385-Membrane Glycoproteins, pubmed-meshheading:9973385-Mice, pubmed-meshheading:9973385-Molecular Sequence Data, pubmed-meshheading:9973385-Phosphorylation, pubmed-meshheading:9973385-Protein Binding, pubmed-meshheading:9973385-Protein Tyrosine Phosphatase, Non-Receptor Type 11, pubmed-meshheading:9973385-Protein Tyrosine Phosphatase, Non-Receptor Type 6, pubmed-meshheading:9973385-Protein Tyrosine Phosphatases, pubmed-meshheading:9973385-Receptors, Immunologic, pubmed-meshheading:9973385-SH2 Domain-Containing Protein Tyrosine Phosphatases, pubmed-meshheading:9973385-Signal Transduction, pubmed-meshheading:9973385-Tyrosine, pubmed-meshheading:9973385-src Homology Domains
pubmed:year
1999
pubmed:articleTitle
Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B.
pubmed:affiliation
Howard Hughes Medical Institute, Rheumatology Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't