MST1 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 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Autophagy; EC 2.7.11.1; Kinase, protein; MST subfamily; Protein kinase, STE; Protein kinase, Ser/Thr (non-receptor); STE group; STE20 family
Chromosomal Location of Human Ortholog: 20q13.12
Cellular Component:  cytoplasm; cytosol; nuclear body; nucleoplasm; nucleus; protein-containing complex
Molecular Function:  ATP binding; identical protein binding; magnesium ion binding; protein binding; protein dimerization activity; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activator activity; protein serine/threonine kinase activity; transcription factor binding
Biological Process:  apoptotic process; branching involved in blood vessel morphogenesis; cell differentiation involved in embryonic placenta development; cell morphogenesis; central nervous system development; endocardium development; hepatocyte apoptotic process; hippo signaling; intracellular signal transduction; keratinocyte differentiation; negative regulation of canonical Wnt signaling pathway; negative regulation of cell proliferation; negative regulation of organ growth; neural tube formation; peptidyl-serine phosphorylation; positive regulation of apoptotic process; positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; positive regulation of fat cell differentiation; positive regulation of peptidyl-serine phosphorylation; positive regulation of protein binding; positive regulation of protein phosphorylation; positive regulation of protein serine/threonine kinase activity; positive regulation of vascular associated smooth muscle cell apoptotic process; primitive hemopoiesis; protein autophosphorylation; protein phosphorylation; protein stabilization; regulation of cell differentiation involved in embryonic placenta development; signal transduction
Disease: T-cell Immunodeficiency, Recurrent Infections, And Autoimmunity With Or Without Cardiac Malformations
Reference #:  Q13043 (UniProtKB)
Alt. Names/Synonyms: dJ211D12.2 (serine/threonine kinase 4 (MST1, KRS2)); DKFZp686A2068; hippo homolog; kinase responsive to stress 2; KRS2; Mammalian STE20-like protein kinase 1; mammalian sterile 20-like 1; MST-1; MST1; MST1/C; MST1/N; serine/threonine kinase 4; Serine/threonine-protein kinase 4; Serine/threonine-protein kinase 4 18kDa subunit; Serine/threonine-protein kinase 4 37kDa subunit; Serine/threonine-protein kinase Krs-2; STE20-like kinase MST1; STK4; yeast Ste20-like; YSK3
Gene Symbols: STK4
Molecular weight: 55,630 Da
Basal Isoelectric point: 4.97  Predict pI for various phosphorylation states
CST Pathways:  Hippo Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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MST1

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