Cyclin E and cyclin A are likely targets of Src for PDGF-induced DNA synthesis in fibroblasts.

How tyrosine kinases of the Src family regulate platelet-derived growth factor (PDGF)-induced DNA synthesis remains elusive. Here we show that the E1A antigen of adenovirus 5 overrides the G1 block elicited by the kinase-inactive mutant SrcK(-). This was dependent upon the CR2 region of E1A that upregulated cyclin E and cyclin A and inactivated the pocket protein pRb. E1A rescue was independent of pRb. Expression of SrcK(-) in fibroblasts prevented PDGF-induced expression of cyclins E and A. This effect was overcome by E1A. Constitutive expression of cyclins E and A, but not D1, restored mitogenesis that was inhibited by SrcK(-). We conclude that both cyclin E and cyclin A are likely targets of Src mediating PDGF-induced DNA synthesis.