DIFFERENTIAL-EFFECTS OF CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE ON P70 RIBOSOMAL S6 KINASE

cAMP exerts differential effects on mitogenic signaling pathways. In m any cells, cAMP inhibits growth factor-stimulated MAPK activity and pr oliferation. In others, cAMP promotes growth. TSH stimulates prolifera tion through elevations in cAMP in thyroid follicular cells. This mito genic pathway is dependent upon both protein kinase A and Ras, but not upon Raf-1, mitogen-activated protein kinase kinase, or mitogen-activ ated protein kinase. We report that TSH, acting through cAMP, activate s pp70(s6k) and that this activity is required for TSH-stimulated DNA synthesis. A similar role for pp70(s6k) in cAMP-mediated mitogenesis w as observed in secondary rat Schwann cells and in Swiss3T3 fibroblasts , two additional cell types that respond to cAMP with growth. In contr ast, cAMP elevation did not activate pp70(s6k) in NIH3T3 or REF52 fibr oblasts, cells in which cAMP fails to stimulate proliferation. Togethe r, these results suggest that pp70(s6k) plays an important and general role in cAMP-mediated proliferation.