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Platelet-derived growth factor increases the turnover of GTP/GDP on Ras in permeabilized fibroblasts
Department of Pathology, University Hospital, Uppsala, Sweden.ORCID iD: 0000-0001-8889-5803
Department of Pathology, University Hospital, Uppsala, Sweden.
1993 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 268, no 24, p. 18187-18194Article in journal (Refereed) Published
Abstract [en]

The potent mitogen platelet-derived growth factor (PDGF) induced a rapid increase in Ras.GTP in permeabilized human and murine fibroblasts. The effect was initiated by both PDGF-AA acting exclusively through PDGF alpha-receptors, and by PDGF-BB interacting with both alpha- and beta-type receptors. The dose-response curves suggest that both receptor types mediate the response. PDGF-dependent Ras activation, measured as increased formation of Ras.GTP, was rapid and reversible. At 37 degrees C the effect had a duration of around 10 min. The PDGF-dependent increase in Ras.GTP was followed by a simultaneous increase in Ras.GDP. Under no experimental condition could a relative increase in Ras.GTP be detected. 0.5 microM GDP and 0.5 microM GTP were equally potent competing for the formation of Ras.[alpha-32P]GTP upon PDGF stimulation. Furthermore, when the basal nucleotide exchange rate on Ras was elevated by omission of Mg2+ from the medium, PDGF had no further effect on the formation of Ras.GTP. We therefore conclude that PDGF activates Ras through a mechanism leading to an increased nucleotide exchange on Ras.

Place, publisher, year, edition, pages
The American Society for Biochemistry and Molecular Biology, Inc. , 1993. Vol. 268, no 24, p. 18187-18194
National Category
Medical and Health Sciences Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:oru:diva-79049ISI: A1993LT74300080PubMedID: 8349694Scopus ID: 2-s2.0-0027219341OAI: oai:DiVA.org:oru-79049DiVA, id: diva2:1386270
Funder
Magnus Bergvall Foundation
Note

This work was supported by the Swedish Natural Science Research Council and Magn. Bergvalls Stiftelse (to E. N.).

Available from: 2013-10-21 Created: 2020-01-17 Last updated: 2020-01-27Bibliographically approved

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