Physiological Reviews, Vol. 79, No. 4, October 1999, pp. 1283-1316
Copyright ©1999 by the American Physiological Society
Mechanism of Action and In Vivo Role of Platelet-Derived
Growth Factor
Carl-Henrik
Heldin and
Bengt
Westermark
Ludwig Institute for Cancer Research, Biomedical Center, and
Department of Pathology, University Hospital, Uppsala,
Sweden
Heldin, Carl-Henrik and
Bengt Westermark.
Mechanism of Action and In Vivo Role of Platelet-Derived
Growth Factor. J. Neurophysiol. 79: 1283-1316, 1999. Platelet-derived growth
factor (PDGF) is a major mitogen for connective tissue cells and
certain other cell types. It is a dimeric molecule consisting of
disulfide-bonded, structurally similar A- and B-polypeptide
chains, which combine to homo- and heterodimers. The PDGF isoforms
exert their cellular effects by binding to and activating two
structurally related protein tyrosine kinase receptors, denoted the
-receptor and the 
-receptor. Activation of PDGF receptors leads
to stimulation of cell growth, but also to changes in cell shape and
motility; PDGF induces reorganization of the actin filament system and
stimulates chemotaxis, i.e., a directed cell movement toward a gradient
of PDGF. In vivo, PDGF has important roles during the embryonic
development as well as during wound healing. Moreover, overactivity of
PDGF has been implicated in several pathological conditions. The
sis oncogene of simian sarcoma virus (SSV) is related to the
B-chain of PDGF, and SSV transformation involves autocrine
stimulation by a PDGF-like molecule. Similarly, overproduction of
PDGF may be involved in autocrine and paracrine growth stimulation of
human tumors. Overactivity of PDGF has, in addition, been implicated in
nonmalignant conditions characterized by an increased cell
proliferation, such as atherosclerosis and fibrotic conditions. This
review discusses structural and functional properties of PDGF and PDGF
receptors, the mechanism whereby PDGF exerts its cellular effects, and
the role of PDGF in normal and diseased tissues.
