Recombinant human STK3/MST-2 protein (GST tag N-Terminus)

General info

Function

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation (PubMed : 11278283, PubMed : 8566796, PubMed : 8816758). Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed : 15688006, PubMed : 16930133, PubMed : 23972470, PubMed : 28087714, PubMed : 29063833, PubMed : 30622739). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed : 15688006, PubMed : 16930133, PubMed : 23972470, PubMed : 28087714). STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250 (PubMed : 21076410, PubMed : 21723128). In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (PubMed : 21104395). Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259' (PubMed : 20212043). Phosphorylates MOBKL1A and RASSF2 (PubMed : 19525978). Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38 (PubMed : 18328708, PubMed : 18362890).

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Post-translational modifications

Autophosphorylated on two residues Thr-174 and Thr-180, leading to activation (PubMed:23972470, PubMed:29063833). Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1. Phosphorylated at Ser-15 by PLK1, leading to activation (PubMed:21723128). When autophosphorylated at Thr-180, recruits STRIPAK complex and promotes PP2A-mediated dephosphorylation and inactivation of STK3 (PubMed:29063833, PubMed:30622739).. Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N).. Ubiquitinated by TRIM69; leading to its redistribution to the perinuclear cytoskeleton, where it is phosphorylated by PLK1 and subsequently activated.