Downregulation of platelet-derived growth factor receptor-beta in Shp-2 mutant fibroblast cell lines - PubMed (original) (raw)

. 1998 Jul 30;17(4):441-8.

doi: 10.1038/sj.onc.1201988.

Affiliations

Downregulation of platelet-derived growth factor receptor-beta in Shp-2 mutant fibroblast cell lines

X Lu et al. Oncogene. 1998.

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 beta subunit of platelet-derived growth factor receptor (PDGFR-beta) was specifically downregulated in mutant fibroblasts lacking a functional Shp-2, while the levels of PDGFR-alpha 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-beta but not PDGFR-alpha, was not phosphorylated on tyrosine in mutant cells upon PDGF-treatment. Northern blot analysis failed to detect PDGFR-beta mRNA in mutant cells. The transcription initiation from the PDGFR-beta 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-beta expression. We propose that this is an important mechanism for the positive control of cell proliferation by Shp-2.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources