Association and direct activation of signal transducer and activator of transcription1α by platelet-derived growth factor receptor

Goutam Ghosh Choudhury, Nandini Ghosh-Choudhury, Hanna E. Abboud

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

PDGF stimulates tyrosine phosphorylation of Janus kinase 1 (JAK1) and the signal transducer and activator of transcription 1 (STAT1α). However, it is not known whether JAKs are required for STAT1α phosphorylation or if the PDGF receptor itself can directly tyrosine phosphorylate and activate STAT1α. In vitro immunecomplex kinase assay of PDGF β receptor (PDGFR) or STAT1α immunoprecipitates from lysates of mesangial cells treated with PDGF showed phosphorylation of a 91- and an 185-kD protein. Incubation of lysates prepared from quiescent mesangial cells with purified PDGFR resulted in STAT1α activation. Immunodepletion of Janus kinases from the cell lysate before incubation with the purified PDGFR showed no effect on STAT1α activation. Moreover, lysates from mesangial cells treated with JAK2 inhibitor, retained significant STAT1α activity. To confirm that STAT1α is a substrate for PDGFR, STAT1α protein was prepared by in vitro transcription and translation. The addition of purified PDGFR to the translated STAT1α resulted in its phosphorylation. This in vitro phosphorylated and activated protein also forms a specific protein-DNA complex. Dimerization of the translated STAT1α protein was also required for its DNA binding. Incubation of pure STAT1α with autophosphorylated PDGFR resulted in physical association of the two proteins. These data indicate that activated PDGFR may be sufficient to tyrosine phosphorylate and thus directly activate STAT1α.

Original languageEnglish (US)
Pages (from-to)2751-2760
Number of pages10
JournalJournal of Clinical Investigation
Volume101
Issue number12
DOIs
StatePublished - Jun 15 1998

Keywords

  • Mesangial cells
  • PDGFR
  • STAT1α

ASJC Scopus subject areas

  • Medicine(all)

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