Department of Pathology , University of Washington , Seattle 98195 .
Trends Genet 7 : 413-8 ( 1991)
Abstract
Platelet-derived growth factor ( PDGF ) has been proposed to be one of the growth factors that drive proliferation during normal development and in various pathological conditions .
Support for these hypotheses has been largely circumstantial .
We discuss the pros and cons of the different experimental approaches that have been taken to test these hypotheses , and evaluate the information to be gained by characterizing the consequences of deletion of one of the PDGF receptor genes in the Patch mutant mouse .
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Department of Pathology , Albert Einstein College of Medicine , Bronx , New York 10461 .
Cell Immunol 143 : 118-26 ( 1992)
Abstract
Human vascular endothelial cells secrete platelet-derived growth factor ( PDGF)-like polypeptides which may mediate some of the vascular effects in the inflammatory process .
We have demonstrated that IL-6 caused a significant increase in the mRNA level of the c-sis gene ( PDGF B chain ) in cultured human endothelial cells .
IL-1 alpha and IL-1 beta also increased c-sis mRNA transcripts after an extended incubation period and both cytokines acted synergistically with IL-6 in increasing c-sis expression .
Tumor necrosis factor enhanced the accumulation of c-sis mRNA and interferon-gamma decreased its level .
In the inflammatory process specific cytokines can modulate c-sis expression in human endothelial cells .
Their subsequent production of PDGF-like polypeptides could stimulate cell migration and proliferation , and cause the release of vascular inflammatory mediators .
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Department of Cellular Biochemistry , Central Institute of Molecular Biology , BerlinBuch , Germany .
Biochem Int 26 : 617-25 ( 1992)
Abstract
The natural tyrosine kinase inhibitor erbstatin and a synthetic analog ( 1302 ) were co0pared for their inhibitory activity on EGF receptor kinase , PDGF receptor kinase and a src-type kinase from bovine brain .
Erbstatin inhibited both growth factor receptor kinases equally well and had little effect on the src kinase .
The analog exhibited similar potency for inhibition of purified EGF receptor tyrosine kinase as erbstatin , however , was clearly less effective for inhibition of purified PDGF receptor kinase as well as the src-type kinase .
The selectivity was , however , not seen when the derivative was assayed with respect to inhibition of autophosphorylation of both growth factor receptors in Swiss 3T3 cell membranes .
The latter finding might explain a lack of selectivity of the compound for inhibition of DNA synthesis in T3 cells when the cells were stimulated comparatively with EGF , insulin , EGF plus insulin or PDGF .
The results suggest that the environment of growth factor receptors in the cell membrane can remarkably modify their susceptibility to tyrosine kinase inhibitors .