Contacts between membrane proximal regions of the PDGF receptor ectodomain are required for receptor activation but not for receptor dimerization.

ABSTRACT: The mechanism of PDGF-receptor beta (PDGFRbeta) activation was explored by analyzing the properties of mutant receptors designed based on the crystal structure of the extracellular region of the related receptor tyrosine kinase KIT/stem cell factor receptor. Here, we demonstrate that PDGF-induced activation of a PDGFRbeta mutated in Arg-385 or Glu-390 in D4 (the fourth Ig-like domain of the extracellular region) was compromised, resulting in impairment of a variety of PDGF-induced cellular responses. These experiments demonstrate that homotypic D4 interactions probably mediated by salt bridges between Arg-385 and Glu-390 play an important role in activation of PDGFRbeta and all type III receptor tyrosine kinases. We also used a chemical cross-linking agent to covalently cross-link PDGF-sti

SUBMITTER: Yang Y 

PROVIDER: S-EPMC2409387 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature