Upregulation of the platelet-derived growth factor (PDGF) receptor- (PDGFR-) is a mechanism of myofibroblast hyperplasia during pulmonary fibrosis. We previously identified interleukin (IL)-1 as a major inducer of the PDGFR- in rat pulmonary myofibroblasts in vitro. In this study, we report that staurosporine, a broad-spectrum kinase inhibitor, upregulates PDGFR- gene expression and protein. A variety of other kinase inhibitors did not induce PDGFR- expression. Staurosporine did not act via an IL-1 autocrine loop because the IL-1 receptor antagonist protein did not block staurosporine-induced PDGFR- expression. Furthermore, staurosporine did not activate a variety of signaling molecules that were activated by IL-1, including nuclear factor-B, extracellular signal-regulated kinase, and c-Jun NH₂-terminal kinase. However, both staurosporine- and IL-1-induced phosphorylation of p38 mitogen-activated protein kinase and upregulation of PDGFR- by these two agents was inhibited by the p38 inhibitor SB-203580. Finally, staurosporine inhibited basal and PDGF-stimulated mitogenesis over the same concentration range that induced PDGFR- expression. Collectively, these data demonstrate that staurosporine is a useful tool for elucidating the signaling mechanisms that regulate PDGFR expression in lung connective tissue cells and possibly for evaluating the role of the PDGFR- as a growth arrest-specific gene.