RPS6KA3
RPS6KA3 (ribosomal protein S6 kinase A3, also known as RSK2, HU-3, MRX19 and CLS) is a serine/threonine kinase that acts downstream of ERK signalling. It links mitogenic and stress signals to transcription, translation, cell survival and differentiation. Browse Assay Genie's current range of RPS6KA3 research reagents below, or read on for the biology behind the target.
RPS6KA3 is a serine/threonine-protein kinase that acts downstream of ERK1 and ERK2 (MAPK3 and MAPK1). It mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77. In fibroblasts it is required for EGF-stimulated phosphorylation of CREB1 and of histone H3 at Ser-10, leading to activation of several immediate-early genes. It also phosphorylates the cofactor CREBBP and, after insulin signalling, GSK3B at Ser-9, which inhibits GSK3B activity.
The kinase also regulates translation and growth signalling. It phosphorylates RPS6 in response to serum or EGF by an mTOR-independent mechanism, and phosphorylates EIF4B in response to insulin, which stimulates cap-dependent translation. It contributes to mTOR nutrient sensing by phosphorylating TSC2 at Ser-1798 and by phosphorylating RPTOR. For survival and cell cycle control, it phosphorylates BAD, DAPK1 and CDKN1B. Other substrates include SOS1, which feeds back to restrain MAPK1/3 phosphorylation, EPHA2, which affects cell migration, and ATF4, which promotes osteoblast differentiation. In myeloma cells it acts as an effector of FGFR3 transformation signalling.
The RPS6KA3 gene encodes a member of the RSK (ribosomal S6 kinase) family, which belongs to the AGC Ser/Thr protein kinase superfamily and the S6 kinase subfamily. The protein has two non-identical kinase catalytic domains. HGNC places it among the MAPK activated protein kinases. It was formerly named ribosomal protein S6 kinase, 90kD, polypeptide 3. Mutations in the gene are associated with Coffin-Lowry syndrome (CLS), and the mouse ortholog is Rps6ka3.
RPS6KA3 is a downstream effector of ERK1/2 and phosphorylates SOS1 to negatively regulate EGF-induced MAPK1/3 phosphorylation.
It phosphorylates RPS6, EIF4B, TSC2 and RPTOR, making it useful for studying translation initiation and mTORC1 regulation.
By phosphorylating BAD, DAPK1 and CDKN1B, RPS6KA3 modulates survival, apoptosis and G1 progression.
Mutations in the RPS6KA3 gene are associated with Coffin-Lowry syndrome, so the kinase is central to studies of this disorder.
RPS6KA3 is a serine/threonine kinase downstream of ERK1/2. It phosphorylates transcription factors such as CREB1 and NR4A1, translation factors RPS6 and EIF4B, and regulators including TSC2, BAD and CDKN1B. Through these substrates it influences proliferation, survival, differentiation and mTOR signalling.
RPS6KA3 is also called RSK2, HU-3, MRX19 and CLS. Its earlier name was ribosomal protein S6 kinase, 90kD, polypeptide 3. UniProt lists it as ribosomal protein S6 kinase alpha-3. It belongs to the RSK family of kinases.
Yes. NCBI Gene reports that mutations in RPS6KA3 are associated with Coffin-Lowry syndrome (CLS). The mouse ortholog is Rps6ka3, so the gene can be studied in mouse models; check the datasheet of any product for its validated reactivity.
Other ribosomal S6 kinases, MAPK-activated kinases and the ribosomal protein S6 substrate, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P51812; product specifications from Assay Genie datasheets.