MAP2 kinase and 70K S6 kinase lie on distinct signalling pathways.
Activation of protein synthesis is required for quiescent cells to transit the cell cycle, and seems to be mediated in part by phosphorylation of the 40S ribosomal protein, S6. A mitogen-activated S6 kinase of relative molecular mass 70,000 (70K) has been isolated from mouse fibroblasts as well as from avian, rat and rabbit tissues. Comparison of complementary DNA sequences shows that this enzyme is distinct from S6 kinase II (92K) found in Xenopus eggs and fibroblasts. Both kinases are activated by serine/threonine phosphorylation, 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 stimulation. 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 enzyme. These and other findings 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.
Ballou
L M
LM
Friedrich Miescher-Institut, Basel, Switzerland.
Luther
H
H
Thomas
G
G
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001769:Blood; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D004789:Enzyme Activation; D004793:Enzyme Reactivators; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009865:Oocytes / Q000201:enzymology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine; D011494:Protein Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014981:Xenopus
D004793:Enzyme Reactivators; D007328:Insulin; D010769:Phosphothreonine; D010768:Phosphoserine; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases