While it is known that the constitutive activity of a variety of signal transduction molecules leads to cell transformation, a key unresolved question is whether these wirings converge to a common intermediate (s) that dictates transformation. In this study, we investigated whether NIH3T3 and Rat-1 cells transformed by human ornithine decarboxylase (ODC), c-Ha-ras Val12 and temperature-sensitive v-src oncogene display common alteration (s) in the components that relay PDGF-mediated signals in normal fibroblasts. The ras-and ODC-transformed cells did not show constitutively elevated tyrosine phosphorylation of the phospholipase Cγ-1 (PLCγ-1), RasGTPase-activating protein (GAP), phosphotyrosine phosphatase Syp, Shc proteins, and phosphatidylinositol 3-kinase (PI3-K) or activation of the MAP kinase (Erk1 and Erk2), p70 S6 kinase or the Janus protein tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) protein-1 pathways. Instead, the Ras nucleotide exchange factor Sos-1 and Raf-1 kinase exhibited constitutive phosphorylations, as deduced from their electrophoretic mobility shifts in polyacrylamide gels. Hence a kinase distinct from Erk1 and Erk2, previously known to feedback phosphorylate Sos-1 and Raf-1, is responsible for the phosphorylation of these molecules in the transformants. We also demonstrate that the ras-and ODC-transformed cells exhibit loss of both the PDGF α-and β-receptors, while the v-Src-transformants show a predominant reduction in the β-receptors. Moreover, all the transformed cell lines were found to display a constitutive increase in phosphorylation of c-Jun on serines 63 and 73, which appears to be governed by an as yet unknown kinase.