cAMP signaling selectively influences Ras effectors pathways

摘要: Thyrotropin (TSH) stimulates survival and growth of thyroid cells via a seven transmembrane G protein-coupled receptor. TSH elevates the intracellular cyclic AMP (cAMP) levels activating protein kinase A (PKA). Recent evidence indicates that p21 Ras is required for TSH-induced mitogenesis, but molecular mechanism(s) not known. Here we report activity necessary Go- G1 transition in induced cycle downstream effector upon signaling p85-p110 PI3K. We show PI3K inhibitors block DNA synthesis, cAMP-PKA stimulate formation complex PI3K-p21 reduce Ras-Raf1 other types. Moreover, PKA phosphorylates immunoprecipitated p85 phosphorylation cell extracts significantly PI3K-Ras. suggest stabilizes p110-p85, enhancing interaction Ras. Simultaneously, cAMP inhibits Raf-1-ERK by decreasing Raf1 availability to Under these circumstances favored. These results indicate an important mediator effects cAMP-induced proliferation illustrates how can selectively influence pathways.