Abstract
The SH2-containing tyrosine phosphatase Shp-2 appears to function downstream of a variety of growth factor receptors and might play a positive role in cell proliferation. Here we report that expression of the β subunit of platelet-derived growth factor receptor (PDGFR-β) was specifically downregulated in mutant fibroblasts lacking a functional Shp-2, while the levels of PDGFR-α EGFR and IGFIR were not changed. PDGF-stimulated DNA synthesis and extracellular signal regulated kinase (Erk) activation was severely suppressed in mutant cells. RasGAP, that responds to activation of PDGFR-β but not PDGFR-α, was not phosphorylated on tyrosine in mutant cells upon PDGF-treatment. Northern blot analysis failed to detect PDGFR-β mRNA in mutant cells. The transcription initiation from the PDGFR-β gene promoter was not significantly changed, but the half-life of its mRNA was shortened in Shp-2 mutant cells. These observations indicate that Shp-2 not only participates in transmission of signals from growth factor receptors but also plays a specific role in the control of the PDGFR-β expression. We propose that this is an important mechanism for the positive control of cell proliferation by Shp-2.
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lu, X., Qu, CK., Shi, ZQ. et al. Downregulation of platelet-derived growth factor receptor-β in Shp-2 mutant fibroblast cell lines. Oncogene 17, 441–448 (1998). https://doi.org/10.1038/sj.onc.1201988
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201988
- Springer Nature Limited
Keywords
This article is cited by
-
ATL‐1, an analogue of aspirin‐triggered lipoxin A4, is a potent inhibitor of several steps in angiogenesis induced by vascular endothelial growth factor
British Journal of Pharmacology (2008)
-
SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis
Oncogene (1999)