y. Cell Sci. Suppl. 3, 65-76 (1985) Printed in Great Britain © The Company of Biologists Limited 1985 65 PLATELET-DERIVED GROWTH FACTOR: MECHANISM OF ACTION AND RELATION TO ONCOGENES C .-H . H E L D IN 1’*, C . B E T SH O L T Z 2, A . JO H N SSO N 1, M . N IS T E R 2, B . E K 1, L . R O N N ST R A N D 1, A. W A ST ESO N 3 and B. W ESTERMARK2 1 Department of M edical and Physiological Chemistry, Box 575, Biomedical Center, S-751 23 Uppsala, Sweden 2 Department of Pathology, University Hospital, S-751 85 Uppsala, Sweden 3Clinical Research Center, University Hospital, S-581 85 Linköping, Sweden SUMMARY Recent studies of platelet-derived growth factor (PD G F) have revealed several structural and functional similarities between this growth factor or components linked to its mechanism of action and certain oncogene products: PD G F itself has a structural homology with the transforming protein of simian sarcoma virus, the PD G F receptor has a functional homology (tyrosine kinase activity) w ith a family of oncogene products, and PD G F induces the expression of the cellular counterparts of myc and fos. In addition, several tumour cell lines have been found to produce PDGF-like growth factors, which may cause autocrine stimulation of growth. We interpret these findings as indicating that regulatory components along the PDGF-dependent mitogenic pathway may have oncogenic properties if they are inappropriately expressed or activated. IN T R O D U C T IO N Platelet-derived growth factor (PDGF) is the major mitogen in serum for con nective tissue-derived cells (for a recent review on PD G F, see H eldin, W asteson & W esterm ark, 1985). The in vivo function of PDGF is not known, but it has been speculated that it has a role in normal as w ell as pathological cell proliferation, e.g. in conjunction with wound healing, atherosclerosis, myelofibrosis and neoplasia. Our m ajor interest in PD G F research com es from studies on the control of grow th of cells in culture. Several recent findings link growth factors and components involved in their mechanism of action to oncogene products. As will be reviewed in this article, studies on PD G F have been particularly illustrative in this context. THE STRUCTURE OF PDGF AND ITS RELATION TO p 2 8 sls The native PDGF-molecule has an Mr of-about 30X103 and consists of two different disulphide-bonded polypeptide chains of similar size, designated A and B (Johnsson, Heldin, Westermark & Wasteson, 1982). The molecule is probably a heterodimer of one A chain and one B chain, but the existence of homodimers A—A and B—B has not been ruled out. A dimer structure for PD G F appears to be im portant for the m itogenic activity, since reduction irreversibly inactivates PD G F. * Author for correspondence.