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rdf:type |
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lifeskim:mentions |
umls-concept:C0031715,
umls-concept:C0040005,
umls-concept:C0205145,
umls-concept:C0285558,
umls-concept:C0812228,
umls-concept:C0851285,
umls-concept:C1167622,
umls-concept:C1335204,
umls-concept:C1416498,
umls-concept:C1418440,
umls-concept:C1511625,
umls-concept:C1533691,
umls-concept:C1705328,
umls-concept:C1705341
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pubmed:issue |
40
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pubmed:dateCreated |
2000-10-23
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pubmed:abstractText |
The mechanism of outside-in signaling by integrins parallels that for growth factor receptors. In both pathways, phosphorylation of a cytoplasmic segment on tyrosine generates a docking site for proteins containing Src homology 2 (SH2) and phosphotyrosine binding domains. We recently observed that phosphorylation of a threonine (Thr-753), six amino acids proximal to tyrosine 759 in beta(3) of the platelet specific integrin alpha(IIb)beta(3), inhibits outside-in signaling through this receptor. We hypothesized that the presence of phosphothreonine 753 either renders beta(3) a poor substrate for tyrosine kinases or inhibits the docking capabilities of the tyrosyl-phosphorylated form of beta(3.) The first alternative was tested by comparing the phosphorylation of beta(3) model peptides by the tyrosine kinase pp60(c-src) and we found that the presence of a phosphate group on a residue corresponding to Thr-753 did not detectably alter the kinetics of tyrosine phosphorylation. However, the presence of phosphate on this threonine inhibited the binding of Shc to tyrosyl-phosphorylated beta(3) peptide. The inhibitory effect of the phosphate group could be mimicked by substituting an aspartic acid for Thr-753, suggesting that a negative charge at this position modulates the binding of Shc and possibly other phosphotyrosine binding domain- and SH2-containing proteins. A survey of several protein kinases revealed that Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules.
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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/3-phosphoinositide-dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2 Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin beta3,
http://linkedlifedata.com/resource/pubmed/chemical/Intramolecular Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/Threonine,
http://linkedlifedata.com/resource/pubmed/chemical/calyculin A,
http://linkedlifedata.com/resource/pubmed/chemical/squalene-hopene cyclase
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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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 |
6
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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 |
30901-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10896934-Amino Acid Sequence,
pubmed-meshheading:10896934-Antigens, CD,
pubmed-meshheading:10896934-Binding Sites,
pubmed-meshheading:10896934-Blood Platelets,
pubmed-meshheading:10896934-Blotting, Western,
pubmed-meshheading:10896934-CDC2 Protein Kinase,
pubmed-meshheading:10896934-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:10896934-Enzyme Activation,
pubmed-meshheading:10896934-Humans,
pubmed-meshheading:10896934-Integrin beta3,
pubmed-meshheading:10896934-Intramolecular Transferases,
pubmed-meshheading:10896934-Kinetics,
pubmed-meshheading:10896934-Molecular Sequence Data,
pubmed-meshheading:10896934-Mutagenesis, Site-Directed,
pubmed-meshheading:10896934-Oxazoles,
pubmed-meshheading:10896934-Peptides,
pubmed-meshheading:10896934-Phosphorylation,
pubmed-meshheading:10896934-Phosphotyrosine,
pubmed-meshheading:10896934-Platelet Aggregation,
pubmed-meshheading:10896934-Platelet Membrane Glycoproteins,
pubmed-meshheading:10896934-Protein Binding,
pubmed-meshheading:10896934-Protein Kinase C,
pubmed-meshheading:10896934-Protein Structure, Tertiary,
pubmed-meshheading:10896934-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10896934-Protein-Tyrosine Kinases,
pubmed-meshheading:10896934-Proto-Oncogene Proteins,
pubmed-meshheading:10896934-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:10896934-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:10896934-Signal Transduction,
pubmed-meshheading:10896934-Threonine,
pubmed-meshheading:10896934-Time Factors,
pubmed-meshheading:10896934-src Homology Domains
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pubmed:year |
2000
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pubmed:articleTitle |
Threonine phosphorylation of the beta 3 integrin cytoplasmic tail, at a site recognized by PDK1 and Akt/PKB in vitro, regulates Shc binding.
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pubmed:affiliation |
Department of Cell Biology & Anatomy, New York Medical College, Valhalla, New York 10595, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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