Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (PDGF) receptor (PDGFR) have been found in patients with scleroderma and are responsible for the activation of skin fibroblasts, we tested the hypothesis that these autoant...

OBJECTIVE It has been suggested that autoantibodies in systemic sclerosis (SSc) may induce the differentiation of cultured fibroblasts into myofibroblasts through platelet-derived growth factor receptor (PDGFR) activation. The present study aims to characterize the effects of SSc IgG on vascular smooth muscle cells (VSMCs) and to determine if stimulatory autoantibodies directed to the PDGFR can...

Metastasis is the major cause of cancer morbidity, but strategies for direct interference with invasion processes are lacking. Dedifferentiated, late-stage tumor cells secrete multiple factors that represent attractive targets for therapeutic intervention. Here we show that metastatic potential of oncogenic mammary epithelial cells requires an autocrine PDGF/PDGFR loop, which is established as ...

PDGF stimulates tyrosine phosphorylation of Janus kinase 1 (JAK1) and the signal transducer and activator of transcription 1 (STAT1alpha). However, it is not known whether JAKs are required for STAT1alpha phosphorylation or if the PDGF receptor itself can directly tyrosine phosphorylate and activate STAT1alpha. In vitro immunecomplex kinase assay of PDGF beta receptor (PDGFR) or STAT1alpha immu...

Infection by human cytomegalovirus (HCMV) is associated with the development of vascular diseases and may cause severe brain damage in infected fetuses. Platelet-derived growth factor receptors alpha and beta (PDGFR-alpha and -beta) control important cellular processes associated with atherosclerosis and fetal development. In the present investigation, our goal was to determine whether infectio...

Signaling by the platelet-derived growth factor receptor(PDGFR ) is diminished when the PDGFR is phosphorylated on seryl residues by G protein-coupled receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the PDGFR remain obscure. We therefore tested whether the PDGFR is able to tyrosinephosphorylate and thereby activate GRK5. Purified GRK5 was tyrosine-phosphorylated by the wild-type...