HD-PTP is important for platelet-derived growth factor beta-receptor downregulation and mitogenicity
(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
HD-PTP (His domain-protein tyrosine phosphatase) is a ubiquitously expressed, putative protein tyrosine phosphatase that has been implicated in regulation of cell migration and endosomal sorting of epidermal growth factor receptor (EGFR), and in multivesicular bodies formation. In this study we show that silencing of HD-PTP negatively regulates the PDGF- induced phosphorylation of the ubiquitin ligase c-Cbl, which was associated with lower PDGFRβ ubiquitination. We also showed that in cells depleted of HD-PTP, PDGFRβ degradation but not cell-surface clearance was decreased. Interestingly, our data showed that lack HD-PTP in cells negatively affected PDGF- induced phosphorylation of Erk1/2, Akt and p38 pathways. However, reduced HD-PTP expression resulted in increased proliferative response of cell treated with PDGF. Our data suggests that HD-PTP functions downstream of the PDGFR, affecting c-Cbl phosphorylation, PDGFRβ degradation and signaling.
PDGF, HD-PTP, ubiquitination, downregulation, degradation, c-Cbl, proliferation
IdentifiersURN: urn:nbn:se:uu:diva-123093OAI: oai:DiVA.org:uu-123093DiVA: diva2:312021