MAP2 KINASE AND 70K-S6 KINASE LIE ON DISTINCT SIGNALING PATHWAYS

ACTIVATION of protein synthesis is required for quiescent cells to transit the cell cycle1, and seems to be mediated in part by phosphorylation of the 40S ribosomal protein, S6 (ref. 2). A mitogen-activated S6 kinase of relative molecular mass 70,000 (70K) has been isolated from mouse fibroblasts3,4 as well as from avian, rat and rabbit tissues5-9. Comparison of complementary DNA sequences shows that this enzyme10 is distinct from S6 kinase II (92K)11 found in Xenopus eggs12 and fibroblasts13,14. Both kinases are activated by serine/threonine phosphorylation3,15-18, suggesting that at least one serine/threonine kinase links receptor tyrosine kinases with S6 kinases. A candidate for this link is MAP2 kinase, which is rapidly activated by tyrosine/threonine phosphorylation following mitogenic stimulation19-23. Incubation of MAP2 kinase from insulin-treated 3T3-L1 adipocytes with phosphatase-inactivated S6 kinase II from Xenopus leads to partial reactivation and phosphorylation of the enzyme17. These and other findings8 have led to the suggestion that MAP2 kinase also activates the 70K S6 kinase. Here we refute this idea by showing that the two kinases lie on distinct signalling pathways.