Source:http://linkedlifedata.com/resource/pubmed/id/10473595
Switch to
Predicate | Object |
---|---|
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-meshheading:10473595-Animals,
pubmed-meshheading:10473595-Base Sequence,
pubmed-meshheading:10473595-Cell Line,
pubmed-meshheading:10473595-DNA Primers,
pubmed-meshheading:10473595-Humans,
pubmed-meshheading:10473595-Mice,
pubmed-meshheading:10473595-Protein Tyrosine Phosphatases,
pubmed-meshheading:10473595-Signal Transduction,
pubmed-meshheading:10473595-Substrate Specificity,
pubmed-meshheading:10473595-Ultraviolet Rays
|
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
|