Recombinant human Rsk 2 / MAPKAP Kinase 1b (mutated L608F) protein

Specifications

Form

Liquid

Additional notes

Affinity purified.

General info

Function

Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed : 16213824, PubMed : 16223362, PubMed : 17360704, PubMed : 9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed : 10436156, PubMed : 9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed : 16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed : 8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed : 17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed : 18508509, PubMed : 18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed : 18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed : 16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed : 18508509, PubMed : 18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed : 26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity).

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.

Post-translational modifications

Activated by phosphorylation at Ser-227 by PDPK1. Autophosphorylated on Ser-386, as part of the activation process. May be phosphorylated at Thr-365 and Ser-369 by MAPK1/ERK2 and MAPK3/ERK1. Can also be activated via phosphorylation at Ser-386 by MAPKAPK2.. N-terminal myristoylation results in an activated kinase in the absence of added growth factors.

Subcellular localisation

Nucleus