Open AccessMutations of the platelet-derived growth factor receptor that cause a loss of ligand-induced conformational change, subtle changes in kinase activity, and impaired ability to stimulate DNA synthesis.
Author(s) -
W J Fantl,
Jaime A. Escobedo,
Lewis T. Williams
Publication year - 1989
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.9.10.4473
Subject(s) - biology , platelet derived growth factor receptor , autophosphorylation , dna synthesis , receptor tyrosine kinase , mutant , microbiology and biotechnology , tyrosine kinase , tyrosine phosphorylation , chinese hamster ovary cell , signal transduction , tyrosine , biochemistry , phosphorylation , receptor , growth factor , protein kinase a , dna , gene
The wild-type and two mitogenic-defective mutants of the type beta receptor for platelet-derived growth factor (PDGF) were expressed in Chinese hamster ovary cells. In the first mutant, delta Ki, 82 of 104 amino acids in the kinase insert region were deleted. This mutant was recently reported to be defective in mediating DNA synthesis. In the second mutant, Y825F, tyrosine 825 was converted to phenylalanine by a point mutation. We report here that this mutant is also defective in mediating PDGF-stimulated DNA synthesis. Both mutants were capable of eliciting many of the early responses to PDGF, including receptor autophosphorylation. However, neither mutant was capable of undergoing PDGF-stimulated change in receptor conformation or of phosphorylating exogenous substrate in an in vitro assay. These data suggest that changes in receptor conformation and efficient utilization of specific tyrosine kinase substrates are important for the stimulation of cell proliferation of PDGF and that phosphorylation of tyrosine 825 may be involved in signal transduction.