Two monoclonal antibodies against the receptor for platelet-derived growth factor (PDGF) were obtained by immunizing mice with pure PDGF receptor preparations derived from porcine uterus. The antibodies, denoted PDGFR-B1 and PDGFR-B2, both bound to the external domain of the receptor, as demonstrated by indirect immunofluorescence and binding of 125I-labeled antibodies to intact human fibroblas...

The cytoplasmic tyrosine kinases of the Src family (SFK) play important roles in cell responses induced by growth factors, including cell growth, survival and migration. Here, we review how SFK participate in PDGF (platelet-derived growth factor) receptor signalling leading to DNA synthesis and actin assembly. Furthermore, evidence for a spatial compartmentalization of SFK signalling is also di...

Platelet-derived growth factor (PDGF)-D is a PDGF receptor β (PDGFRβ)-specific ligand implicated in a number of pathological conditions, such as cardiovascular disease and cancer, but its biological function remains incompletely understood. In this study, we demonstrate that PDGF-D binds directly to neuropilin 1 (NRP1), in a manner that requires the PDGF-D C-terminal Arg residue. Stimulation wi...

The outcome of patients with unresectable or metastatic soft tissue sarcoma (STS) remains poor with few treatment options. A number of randomized trials in the first-line setting have shown no difference in overall survival between combination anthracycline schedules and single-agent doxorubicin. A Phase Ib/randomized Phase II trial of doxorubicin with or without the platelet-derived growth fac...

32D cells transfected with the human alpha platelet-derived growth factor receptor (alpha PDGFR) bind PDGF-AA, -AB, and -BB isoforms with high affinity, and the binding of each can be efficiently competed by all three isoforms. In an effort to develop better understanding of spatial relationships of binding sites for PDGF-AA and -BB, we constructed an alpha PDGFR mutant which deleted amino acid...

Autocrine expression of a growth factor and its receptor in the same cell raises the possibility of an intracellular receptor-ligand interaction within the cell, in addition to a receptor-ligand interaction at the cell surface. We have constructed a NIH3T3 cell line which contains the v-sis gene under the inducible control of the Drosophila melanogaster hsp70 promoter. Expression of both v-sis ...

There is strong and consistent evidence from in vitro studies that disturbed blood flow produces a proatherogenic vascular endothelial phenotype. However, data from human studies are lacking. To address this, a 220 mm Hg occlusion cuff was placed on the distal forearm of 10 young, healthy men to induce a localized region of disturbed blood flow in the proximal vasculature for 20 minutes. We hyp...

Injury of an artery by passage of a balloon catheter causes both endothelial denudation and medial damage and produces a marked smooth muscle cell (SMC) proliferative response. In this study, the endothelium from rat carotid arteries was removed by use of a rotating loop of 5/0 monofilament suture (gentle denudation technique), which did not cause any detectable damage to the underlying medial ...

The alpha- and beta-subunits of the receptor for platelet-derived growth factor (PDGFR) were found to be autophosphorylated in the absence of ligands at high expression levels which suggests a propensity of PDGFRs to dimerize spontaneously. When the extracellular domains (ED) of both receptors were expressed and purified to homogeneity, they could be dimerized specifically by the different PDGF...

The thymus provides a specialized site for the production of T cells capable of recognizing foreign antigens in the context of self-major histocompatibility complex (MHC) molecules. During development, the thymus arises from an epithelial rudiment containing bipotent progenitors that differentiate into distinct cortical and medullary epithelial cells to regulate the maturation and selection of ...