Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic andstress-induced activation of the transcription factors CREB1, ETV1/ER81and NR4A1/NUR77, regulates translation through RPS6 and EIF4Bphosphorylation, and mediates cellular proliferation, survival, anddifferentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', whichresults in the subsequent transcriptional activation of severalimmediate-early genes. In response tomitogenic stimulation (EGF and PMA), phosphorylates and activatesNR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on thetranscription regulation of several genes by phosphorylating GSK3B at'Ser-9' and inhibiting its activity. PhosphorylatesRPS6 in response to serum or EGF via an mTOR-independent mechanism andpromotes translation initiation by facilitating assembly of thepreinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex andstimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway bydirectly phosphorylating TSC2 at 'Ser-1798', which potently inhibitsTSC2 ability to suppress mTOR signaling, and mediates phosphorylationof RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptoticfunction. Promotes the survival of hepatic stellatecells by phosphorylating CEBPB in response to the hepatotoxin carbontetrachloride (CCl4). Is involved incell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents itstranslocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector ofFGFR3-mediated transformation signaling, after direct phosphorylationat Tyr-529 by FGFR3. Negatively regulates EGF-inducedMAPK1/3 phosphorylation via phosphorylation of SOS1. Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB andYWHAE binding sites and which contribute to the negative regulation ofMAPK1/3 phosphorylation. Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration. Acts as a regulator of osteoblast differentiation bymediating phosphorylation of ATF4, thereby promoting ATF4transactivation activity. [1-4]

MPLAQLADPWQKMAVESPSDSAENGQQIMDEPMGEEEINPQTEEVSIKEIAITHHVKEGHEKADPSQFELLKVLGQGSFGKVFLVKKISGSDARQLYAMKVLKKATLKVRDRVRTKMERDILVEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGTLPFQGKDRKETMTMILKAKLGMPQFLSPEAQSLLRMLFKRNPANRLGAGPDGVEEIKRHSFFSTIDWNKLYRREIHPPFKPATGRPEDTFYFDPEFTAKTPKDSPGIPPSANAHQLFRGFSFVAITSDDESQAMQTVGVHSIVQQLHRNSIQFTDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPTEEIEILLRYGQHPNIITLKDVYDDGKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESGNPESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDAACDIWSLGVLLYTMLTGYTPFANGPDDTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKMLHVDPHQRLTAALVLRHPWIVHWDQLPQYQLNRQDAPHLVKGAMAATYSALNRNQSPVLEPVGRSTLAQRRGIKKITSTAL