Identification of a domain within the carboxyl-terminal region of the βplatelet-derived growth factor (PDGF) receptor that mediates the high transforming activity of PDGF

Aykut Uren, Jin Chen Yu, Weiqun Li, Il Yup Chung, Daruka Mahadevan, Jacalyn H. Piercei, Mohammad A. Heidaran

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We have reported previously that a chimeric platelet-derived growth factor receptor (PDGFR) possessing the ligand binding domain of the αPDGFR and the intracellular domain of the βPDGFR (α340β342R) was markedly more efficient than the wild type αPDGFR (αRWT) in its ability to enhance PDGF-A transforming activity in NIH/ 3T3 fibroblasts. To determine the region within the cytoplasmic domain of βPDGFR that confers this higher transforming activity, we generated several additional α/βPDGFR chimerae. When a chimeric PDGFR possessing the first 933 amino-terminal amino acids from the αPDGFR and the final 165 amino acids from the carboxyl-terminal of the βPDGFR (α933β942R) was cotransfected with the PDGF-A gene into NIH/3T3 cells, it showed a similar high efficiency to enhance PDGF-A chain transforming activity as α340β342R. However, when chimeric PDGFRs in which either the kinase insert domain (αβRKI) or the last 79 amino acids from the carboxyl-terminal end of the βPDGFR (α1024β1028R) were substituted into αPDGFR sequences were cotransfected with PDGF-A, they showed similar low efficiencies in enhancing transforming activity as the αRWT. These results predicted that the 86 amino acids following the tyrosine kinase 2 domain of βPDGFR (amino acid residues 942-1027) were responsible for the higher transforming activity of βPDGFR. To confirm this finding, we next constructed a chimera in which amino acid residues 942-1028 of the βPDGFR (αβ942-1028R) were substituted for those in the αPDGFR. Cotransfection experiments indicated that αβ942-1028R increased transforming activity of PDGF-A to similar extent as the α933β942R or α340β342R. Therefore, our findings define a critical do- main within the noncatalytic region of βPDGFR intracellular domain that confers the higher focus forming activity mediated by the βPDGFR.

Original languageEnglish (US)
Pages (from-to)11051-11054
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number19
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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