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.
CRBM, CNRS UPR-1086, 1919 route de Mende, 34293 Montpellier, France.
Olivia
O
Furstoss
Gaël
G
Manes
Serge
S
Roche
D016475:3T3 Cells; D000818:Animals; D019925:Cyclin A / Q000235:genetics*; D019927:Cyclin E / Q000235:genetics*; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D019925:Cyclin A; D019927:Cyclin E; D010982:Platelet-Derived Growth Factor; D016160:Retinoblastoma Protein; D019061:src-Family Kinases