STK3

Protein kinase activation is a frequent response of cells to treatment with growth factors, chemicals, heat shock, or apoptosis-inducing agents. This protein kinase activation presumably allows cells to resist unfavorable environmental conditions. The yeast 'sterile 20' (Ste20) kinase acts upstream of the mitogen-activated protein kinase (MAPK) cascade that is activated under a variety of stress conditions. MST2 was identified as a kinase that is activated by the proapoptotic agents straurosporine and FAS ligand (MIM 134638) (Taylor et al., 1996 [PubMed 8816758]; Lee et al., 2001 [PubMed 11278283]).[supplied by OMIM

serine/threonine kinase 3 (STE20 homolog, yeast)

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. 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. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. 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. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38.

Biological Process apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process canonical Wnt signaling pathwayIEA:Ensembl
Biological Process cell differentiation involved in embryonic placenta developmentIEA:Ensembl
Biological Process central nervous system developmentIEA:Ensembl
Biological Process endocardium developmentIEA:Ensembl
Biological Process epithelial cell proliferationIEA:Ensembl
Biological Process extrinsic apoptotic signaling pathway via death domain receptorsIEA:Ensembl
Biological Process hepatocyte apoptotic processIEA:Ensembl
Biological Process hippo signalingManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process intracellular signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process JNK cascadeIEA:Ensembl
Biological Process negative regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of epithelial cell proliferationIEA:Ensembl
Biological Process negative regulation of organ growthIEA:Ensembl
Biological Process neural tube formationIEA:Ensembl
Biological Process organ growthIEA:Ensembl
Biological Process positive regulation of apoptotic processISS:UniProtKB
Biological Process positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIGI:MGI
Biological Process positive regulation of extrinsic apoptotic signaling pathway via death domain receptorsIEA:Ensembl
Biological Process positive regulation of fat cell differentiationIEA:Ensembl
Biological Process positive regulation of JNK cascadeIEA:Ensembl
Biological Process positive regulation of protein bindingManual Assertion Based On ExperimentIDA:MGI
Biological Process positive regulation of protein kinase B signalingIEA:Ensembl
Biological Process primitive hemopoiesisIEA:Ensembl
Biological Process protein import into nucleusManual Assertion Based On ExperimentIGI:UniProtKB
Biological Process protein kinase B signalingIEA:Ensembl
Biological Process protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein stabilizationManual Assertion Based On ExperimentIMP:MGI
Biological Process protein tetramerizationIEA:InterPro
Biological Process regulation of cell differentiation involved in embryonic placenta developmentIEA:Ensembl
Biological Process regulation of MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Biological Process signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cytoplasm
Nucleus
The caspase-cleaved form cycles between nucleus and cytoplasm (PubMed:19525978, PubMed:11278283).
Phosphorylation at Thr-117 leads to inhibition of nuclear translocation (PubMed:19525978).

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.
Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N).