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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2000-10-13
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pubmed:abstractText |
Signal regulatory proteins (SIRPs) are receptor-like transmembrane proteins, the majority of which contain a cytoplasmic proline-rich region and four cytoplasmic tyrosines that, when phosphorylated, bind SH2 domain-containing protein tyrosine phosphatases (SHP). We demonstrated previously that growth hormone (GH) induces tyrosyl phosphorylation of SIRPalpha and association of SIRPalpha with SHP-2. The GH-activated tyrosine kinase JAK2 associates with and tyrosyl-phosphorylates SIRPalpha1. Here we show that JAK2-SIRPalpha1 association does not require phosphotyrosines in SIRPalpha1 or JAK2 or the proline-rich region of SIRPalpha1. However, when the C-terminal 30 amino acids of SIRPalpha1 containing the proline-rich region and tyrosine 495 are deleted, tyrosyl phosphorylation of SIRPalpha1 by JAK2 and association of SHP-2 with SIRPalpha1 are reduced. GH-dependent tyrosyl phosphorylation of JAK2 is reduced when wild-type SIRPalpha1 compared with SIRPalpha1 lacking the four cytoplasmic tyrosines (SIRP 4YF) is expressed in cells, suggesting that SIRPalpha1 negatively regulates GHR/JAK2 signaling. Consistent with reduced JAK2 activity, overexpression of wild-type SIRPalpha1 but not SIRP 4YF reduces GH-induced phosphorylation of ERKs 1 and 2, STAT3, and STAT5B. These results suggest that SIRPalpha1 is a negative regulator of GH signaling and that the ability of SIRPalpha1 mutants to negatively regulate GHR-JAK2 signaling correlates with their ability to bind SHP-2.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Human Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JAK3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Jak3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Neural Cell Adhesion Molecule L1,
http://linkedlifedata.com/resource/pubmed/chemical/Neural Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Somatotropin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28222-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10842184-3T3 Cells,
pubmed-meshheading:10842184-Animals,
pubmed-meshheading:10842184-Antigens, Differentiation,
pubmed-meshheading:10842184-Cell Line,
pubmed-meshheading:10842184-DNA-Binding Proteins,
pubmed-meshheading:10842184-Enzyme Activation,
pubmed-meshheading:10842184-Human Growth Hormone,
pubmed-meshheading:10842184-Humans,
pubmed-meshheading:10842184-Janus Kinase 2,
pubmed-meshheading:10842184-Janus Kinase 3,
pubmed-meshheading:10842184-Membrane Glycoproteins,
pubmed-meshheading:10842184-Mice,
pubmed-meshheading:10842184-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:10842184-Mitogen-Activated Protein Kinases,
pubmed-meshheading:10842184-Neural Cell Adhesion Molecule L1,
pubmed-meshheading:10842184-Neural Cell Adhesion Molecules,
pubmed-meshheading:10842184-Phosphorylation,
pubmed-meshheading:10842184-Proline,
pubmed-meshheading:10842184-Protein Tyrosine Phosphatases,
pubmed-meshheading:10842184-Protein-Tyrosine Kinases,
pubmed-meshheading:10842184-Proto-Oncogene Proteins,
pubmed-meshheading:10842184-Receptors, Immunologic,
pubmed-meshheading:10842184-Receptors, Somatotropin,
pubmed-meshheading:10842184-Recombinant Proteins,
pubmed-meshheading:10842184-STAT3 Transcription Factor,
pubmed-meshheading:10842184-Sequence Deletion,
pubmed-meshheading:10842184-Signal Transduction,
pubmed-meshheading:10842184-Trans-Activators,
pubmed-meshheading:10842184-Transfection,
pubmed-meshheading:10842184-Tyrosine,
pubmed-meshheading:10842184-src Homology Domains
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pubmed:year |
2000
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pubmed:articleTitle |
Negative regulation of growth hormone receptor/JAK2 signaling by signal regulatory protein alpha.
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pubmed:affiliation |
Department of Microbiology and Immunology and Department of Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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