Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-6-24
pubmed:abstractText
In response to binding of platelet-derived growth factor (PDGF), the PDGF receptor (PDGFR) beta subunit is phosphorylated on tyrosine residues and associates with numerous signal transduction enzymes, including the GTPase-activating protein of ras (GAP) and phosphatidylinositol 3-kinase (PI3K). Previous studies have shown that association of PI3K requires phosphorylation of tyrosine 751 (Y751) in the kinase insert and that this region of receptor forms at least a portion of the binding site for PI3K. In this study, the in vitro binding of GAP to the PDGFR was investigated. Like PI3K, GAP associates only with receptors that have been permitted to autophosphorylate, and GAP itself does not require tyrosine phosphate in order to stably associate with the phosphorylated PDGFR. To define which tyrosine residues are required for GAP binding, a panel of PDGFR phosphorylation site mutants was tested. Mutation of Y771 reduced the amount of GAP that associates to an undetectable level. In contrast, the F771 (phenylalanine at 771) mutant bound wild-type levels of PI3K, whereas the F740 and F751 mutants bound 3 and 23%, respectively, of the wild-type levels of PI3K but wild-type levels of GAP. The F740/F751 double mutant associated with wild-type levels of GAP, but no detectable PI3K activity, while the F740/F751/F771 triple mutant could not bind either GAP or PI3K. The in vitro and in vivo associations of GAP and PI3K activity to these PDGFR mutants were indistinguishable. The distinct tyrosine residue requirements suggest that GAP and PI3K bind different regions of the PDGFR. This possibility was also supported by the observation that the antibody to the PDGFR kinase insert Y751 region that blocks association of PI3K had only a minor effect on the in vitro binding of GAP. In addition, highly purified PI3K and GAP associated in the absence of other cellular proteins and neither cooperated nor competed with each other's binding to the PDGFR. Taken together, these studies indicate that GAP and PI3K bind directly to the PDGFR and have discrete binding sites that include portions of the kinase insert domain.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1314164, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1646396, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1653029, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1661130, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1689011, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1691440, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1696179, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1700866, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1702511, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1703628, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1705010, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1707345, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1708307, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1708916, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1709159, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1710023, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1712671, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1846320, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1848666, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1848725, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1849460, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1849461, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1964089, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-1986867, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2005895, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2122974, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2156626, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2157284, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2158859, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2170111, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2172781, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2173144, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2198577, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2440874, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2441878, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2452172, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2463166, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2466336, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2467744, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2472219, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2475255, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2479827, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2480526, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2538922, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2542288, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2542773, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2550144, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2554305, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2554309, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2631796, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2825654, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2836952, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375321-2842689
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2534-44
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
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