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Cyclin E and cyclin A are likely targets of Src for PDGF‐induced DNA synthesis in fibroblasts
Author(s) -
Furstoss Olivia,
Manes Gaël,
Roche Serge
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03120-4
Subject(s) - cyclin e , cyclin d , cyclin , microbiology and biotechnology , cyclin a , cyclin d1 , platelet derived growth factor receptor , cyclin a2 , cancer research , biology , cyclin dependent kinase complex , cyclin dependent kinase , cyclin b , proto oncogene tyrosine protein kinase src , cell cycle , chemistry , kinase , cyclin dependent kinase 2 , growth factor , biochemistry , cell , protein kinase a , receptor
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.