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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1999-10-7
pubmed:abstractText
UV irradiation of cells causes ligand-independent activation of receptor tyrosine kinases. On the basis of dephosphorylation kinetics, UV-induced inactivation of receptor-directed tyrosine phosphatases (PTP) has been proposed as the mechanism of receptor activation (Knebel, A., Rahmsdorf, H. J., Ullrich, A., and Herrlich, P. (1996) EMBO J. 15, 5314-5325). Here we show that four defined protein-tyrosine phosphatases (PTPs), SHP-1, RPTPalpha, RPTPsigma, and DEP-1, are partially inactivated upon UV irradiation of PTP-overexpressing cells. The dephosphorylation of coexpressed platelet-derived growth factor beta (PDGFbeta) receptor by RPTPalpha is inhibited upon UV irradiation. UV converts RPTPalpha into a substrate-trapping enzyme which can coprecipitate PDGFbeta receptor, similarly to the PTP mutant at the active-center cysteine: C433S. In agreement with the proposed mechanism that inactivation of PTPs accounts for receptor tyrosine kinase activation, no evidence for a UV-induced receptor cross-linking could be obtained in PDGFbeta receptor-enriched membrane micelle preparations and in PDGFbeta receptor overexpressing 293 cells. The intrinsic activity of PDGFbeta receptor kinase was required for the UV-induced enhancement of receptor phosphorylation, but was not changed upon UV irradiation. The data support a mechanism of UV-induced signal transduction involving inactivation of PTPs through an unknown reactive intermediate that oxidizes the conserved cysteine in the active sites of PTPs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26378-86
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Inactivation of protein-tyrosine phosphatases as mechanism of UV-induced signal transduction.
pubmed:affiliation
Research Unit "Molecular Cell Biology," Klinikum der Friedrich Schiller Universität Jena, Drackendorfer Strasse 1, D-07747 Jena, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't