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

Kamil Jastrzębski1, Daria Zdżalik-Bielecka1, Agnieszka Mamińska1

  • 1Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw 02-109, Poland.

Journal of Cell Science
|December 17, 2016
PubMed

Insights

Platelet-derived growth factor receptor β (PDGFRβ) internalization occurs via multiple pathways, including clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE). These distinct routes are crucial for PDGFRβ signaling and cellular responses to PDGF.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Platelet-derived growth factor receptor β (PDGFRβ) is a key regulator of cell proliferation, migration, and angiogenesis.
  • Receptor tyrosine kinase internalization modulates downstream signaling, but PDGFRβ endocytic pathways are not fully elucidated.
  • Previous work identified dynamin-dependent and -independent PDGFRβ internalization, but molecular details were lacking.

Purpose of the Study:

  • To investigate the molecular mechanisms and pathways governing PDGFRβ endocytosis.
  • To determine the contribution of distinct internalization routes to PDGFRβ downstream signaling.
  • To understand how different endocytic pathways influence cellular responses to PDGF-BB.

Main Methods:

  • Human fibroblasts expressing endogenous PDGFRβ were stimulated with PDGF-BB.
  • Endocytosis was studied using clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) inhibitors.
  • Downstream signaling pathways, including STAT3 activation, were analyzed.

Main Results:

  • PDGFRβ uptake occurs via parallel CME and CIE pathways in human fibroblasts.
  • CME involves the AP2 complex, while CIE requires RhoA-ROCK, Cdc42, and galectin-3, suggesting lectin-mediated internalization via CLICs.
  • Inhibition of either CME or CIE impaired STAT3 activation, indicating pathway-specific signaling.
  • Distinct internalization routes are partly interdependent but not fully substitutable.

Conclusions:

  • Multiple endocytic routes contribute to PDGFRβ internalization.
  • Specific internalization pathways differentially regulate PDGFRβ signaling, notably STAT3 activation.
  • Understanding these pathways is crucial for comprehending cellular responses to PDGF.
Keywords:
EndocytosisPDGF-BBPDGFRβPlatelet-derived growth factor BBPlatelet-derived growth factor receptor βRho GTPaseSTAT3Signal transducer and activator of transcription 3

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