Previous studies have shown that platelet-derived growth factor (PDGF) stimulates the phosphorylation of two components in membranes prepared from human fibroblasts in the presence of Ca2+. One of these represents the 185-kDa PDGF receptor, which undergoes autophosphorylation, and the other has an M , of 130000. We show in this communication that the 130-kDa component is derived from the 185-kDa receptor via proteolysis by an endogeneous Ca2+-dependent protease, which is dependent on a reduced -SH group for its activity. The 130-kDa fragment contains several of the characteristics of the receptor, such as the PDGF-binding site and the major autophosphorylation sites. Furthermore, the cleaved receptor retains tyrosine kinase activity.Platelet-derived growth factor, PDGF, is a major mitogen in serum for connective-tissue-derived cells and glial cells (for a recent review on PDGF see [l]). One of the two polypeptide chains of PDGF has recently been shown to be almost identical to part of p28"'", the transforming protein of simian sarcoma virus [2, 31, suggesting that a PDGF-like growth factor is involved in the simian-sarcoma-virus-induced transformation process. PDGF exerts its mitogenic effect via binding to specific high-affinity receptors on responsive cells [4 -81. The binding initiates internalization of the ligand-receptor complex. PDGF, and probably also the receptor are subsequently degraded in the lysosomes [9 -113. The receptor molecule has been identified by affinity labeling and shown to be a single-chain protein of molecular mass around 185 kDa [12-141. The interaction between PDGF and its fibroblast receptor results in stimulation of tyrosine-specific kinase activity [15 -191. Four other growth factors, epidermal growth factor (EGF), insulin, insulin-like growth factor I and colony-stimulating factor-1