Abstract
To determine the molecular basis for the transforming function of platelet-derived growth factor (PDGF)-A in NIH/3T3 cells, we have constructed chimerae consisting of the extracellular domain of the human CSF-1R (fms) linked to the cytoplasmic domain of the alpha PDGF receptor (alpha R) containing a series of deletion or point mutations. The ability of fms/alpha R chimerae to mediate CSF-1-dependent anchorage-independent growth, focus formation, and chemotaxis of NIH/3T3 cells was then examined. Our results provide evidence that a domain encompassing amino acid residues 977-1024 of the alpha PDGFR is required for ligand-dependent focus formation, but not chemotaxis or anchorage-independent growth, and that tyrosine residues within this domain constitute the major binding site for phospholipase C gamma. Therefore, our findings suggest that: (i) the focus forming function of alpha PDGFR correlates well with the ability of the receptor to bind phospholipase C gamma, and (ii) the mechanism of focus formation mediated by alpha PDGFR may be distinguished from that required for chemotaxis or anchorage-independent growth.
Highlights
To determine the molecular basis for the transforming function of platelet-derived growth factor (PDGF)-A in NIH/3T3 cells, we have constructed chimerae consisting of the extracellular domain of the human CSF-IR linked to the cytoplasmic domain ofthe aPDGF receptor containing a series of deletion or point mutations
PDGF dimeric isoforms have been shown to bind with different affinities to two different but related receptor molecules, designated aPDGFR and I3PDGFR, which are en
We sought to further examine the functional role of these domains in a physiologically relevant microenvironment in an attempt to better understand the molecular basis of biological responses mediated by aPDGFR
Summary
1995 Printed in U.S.A. Differential Requirement of a Motif within the Carboxylterminal Domain of a-Plateletderived Growth Factor (aPDGF) Receptor for PDGF Focus Forming Activity Chemotaxis, or Growth*. To determine the molecular basis for the transforming function of platelet-derived growth factor (PDGF)-A in NIH/3T3 cells, we have constructed chimerae consisting of the extracellular domain of the human CSF-IR (fms) linked to the cytoplasmic domain ofthe aPDGF receptor (aR) containing a series of deletion or point mutations. The PDGF-A homodimer mediates biological functions that include chemotaxis, anchorageindependent growth, and focus formation by activating the tyrosine kinase activity of aPDGFR in NIH!3T3 fibroblasts C7-1O). We sought to further examine the functional role of these domains in a physiologically relevant microenvironment in an attempt to better understand the molecular basis of biological responses mediated by aPDGFR
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