PHOSPHORYLATION OF THE 3 RB PROTEIN FAMILY MEMBERS IS A COMMON STEP OF THE CAMP-, THE GROWTH-FACTOR, AND THE PHORBOL ESTER MITOGENIC CASCADES BUT IS NOT NECESSARY FOR THE HYPERTROPHY INDUCED BY INSULIN

Thyrotropin (TSH) through the cAMP cascade and in the presence of insu lin induces the proliferation of dog thyroid cells. In this work, it i s shown that TSH via cAMP causes the phosphorylation of the three memb ers of the pRb family, pRb, p107, and p130, with the same kinetics as those observed when these cells are stimulated by mitogens acting thro ugh a tyrosine kinase receptor or through activation of kinase C. It i s the first described point of convergence of cAMP-dependent and -inde pendent mitogenic pathways in dog thyrocytes and suggests that the pho sphorylation of the three proteins may be involved in the initiation o f DNA synthesis in these cells. We also show that insulin, which induc es hypertrophy and is permissive for the TSH mitogenic action, does no t provoke the phosphorylation of any pRb family member, suggesting tha t none of these phosphorylations is required for this effect. (C) 1997 Academic Press.