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Integrins Enhance Platelet-derived Growth Factor (PDGF)-dependent Responses by Altering the Signal Relay Enzymes That Are Recruited to the PDGF β Receptor
Journal article   Open access   Peer reviewed

Integrins Enhance Platelet-derived Growth Factor (PDGF)-dependent Responses by Altering the Signal Relay Enzymes That Are Recruited to the PDGF β Receptor

Kris A DeMali, Egle Balciunaite and Andrius Kazlauskas
The Journal of biological chemistry, Vol.274(28), pp.19551-19558
07/09/1999
DOI: 10.1074/jbc.274.28.19551
PMID: 10391888
url
https://doi.org/10.1074/jbc.274.28.19551View
Published (Version of record) Open Access

Abstract

Since the extracellular matrix (ECM) can promote platelet-derived growth factor (PDGF)-dependent responses, we hypothesized that the ECM mediates this effect by preventing the PDGF beta receptor (betaPDGFR) from associating with the negative regulator, RasGAP (the GTPase-activating protein of Ras). We found that binding of RasGAP to the wild-type betaPDGFR was decreased; the activation of Ras and Erk was enhanced, and [3H]thymidine uptake was better in cells cultured on fibronectin than in cells cultured on polylysine. To investigate the mechanism by which culturing cells on fibronectin diminished the recruitment of RasGAP to the betaPDGFR, we focused on SHP-2 since it dephosphorylates the betaPDGFR at the phosphotyrosine required for binding of RasGAP. Culturing cells on fibronectin increased the amount of SHP-2 that associated with the betaPDGFR. Furthermore, cells expressing receptor mutants that failed to associate with SHP-2 were insensitive to fibronectin. The ECM enhances PDGF-dependent responses by increasing the association of SHP-2 with the betaPDGFR, which in turn decreases the time that RasGAP interacts with the receptor. Thus, fibronectin changes PDGF-dependent signaling and biological responses by altering the signal relay enzymes that are recruited to the receptor.

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