Multiple routes of endocytic internalization of PDGFRβ contribute to PDGF-induced STAT3 signaling

• DOI: 10.1242/jcs.191213
• Publication Date: 2017-02-01T15:25:26Z
• Authors: Kamil Jastrzębski; Daria Zdżalik-Bie...; Agnieszka Mamińska; Yannis Kalaidzidis; Carina Hellberg; Marta Miaczynska
• Keywords: Internalization; Platelet-derived growth factor

ABSTRACT Platelet-derived growth factor receptor β (PDGFRβ) is a tyrosine kinase which upon activation by PDGF-BB stimulates cell proliferation, migration and angiogenesis. Ligand binding induces intracellular signaling cascades but also internalization of the receptor, eventually resulting in its lysosomal degradation. However, endocytic trafficking receptors often modulates their downstream signaling. We previously reported that PDGFRβ occurs via dynamin-dependent -independent pathways further molecular determinants remained unknown. Here we show that, human fibroblasts expressing endogenous stimulated with 50 ng/ml PDGF-BB, ligand–receptor uptake proceeds parallel routes clathrin-mediated endocytosis (CME) clathrin-independent (CIE). CME involves canonical AP2 complex as clathrin adaptor, while CIE requires RhoA–ROCK, Cdc42 galectin-3, latter indicating lectin-mediated carriers (CLICs). Although different appear to be partly interdependent, they cannot fully substitute for each other. Strikingly, inhibition any mechanism impaired STAT3 not other effectors PDGFRβ. Our data indicate multiple contribute transcriptional mitogenic response cells PDGF.