Summary

Name STK4
Full Name Serine/threonine-protein kinase 4
Synonyms Mammalian STE20-like protein kinase 1, MST-1, STE20-like kinase MST1, Serine/threonine-protein kinase Krs-2 | KRS2, MST1
Primary ID Q13043
Links - -
Type protein
Relations 62
Pathways Hippo Signaling
Function 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 (By similarity). 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.

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png cleavage STK4 0.08
Publications: 2 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png cleavage STK4 0.22
Publications: 2 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation HIST1H2BB 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FOXO3 0.38
Publications: 2 Organism: Homo Sapiens
Tissue: Skin
+ up-regulates img/direct-activation.png phosphorylation FOXO 0.14
Publications: 5 Organism: Homo Sapiens
Tissue: Skin
+ up-regulates img/direct-activation.png phosphorylation FOXO1 0.34
Publications: 2 Organism: Homo Sapiens
Tissue: Skin
+ up-regulates activity img/direct-activation.png phosphorylation STK4 0.34
Publications: 4 Organism: Chlorocebus Aethiops
Pathways:Hippo Signaling
+ up-regulates img/direct-activation.png phosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation LATS2 0.41
Publications: 4 Organism: Homo Sapiens
Pathways:Hippo Signaling
+ up-regulates img/direct-activation.png phosphorylation LATS1 0.36
Publications: 2 Organism: Homo Sapiens
Pathways:Hippo Signaling
+ up-regulates img/direct-activation.png phosphorylation MOB1A 0.56
Publications: 4 Organism: Homo Sapiens
Pathways:Hippo Signaling
+ up-regulates img/direct-activation.png phosphorylation MOB1B 0.56
Publications: 4 Organism: Homo Sapiens
Pathways:Hippo Signaling
+ down-regulates img/direct_inhibition.png phosphorylation STK4 0.38
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STK4 0.14
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation TNNI3 0.31
Publications: 4 Organism: Homo Sapiens
Tissue: Kidney
+ down-regulates img/direct_inhibition.png dephosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation STK4 0.32
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation STK4 0.38
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation ABL1 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding STK4 0.38
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding STK4 0.08
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
+ up-regulates img/direct-activation.png phosphorylation STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png AR 0.08
Publications: 1
+ up-regulates img/direct-activation.png binding STK4 0.56
Publications: 1 Organism: Homo Sapiens
Pathways:Hippo Signaling
+ up-regulates img/direct-activation.png phosphorylation FOXO4 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png STK4 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding STK4 0.47
Publications: 2 Organism: Homo Sapiens
Pathways:Hippo Signaling
+ up-regulates img/direct-activation.png phosphorylation STK4 0.17
Publications: 1 Organism: Homo Sapiens
Pathways:Hippo Signaling
+ up-regulates img/direct-activation.png SAV1 0.41
Publications: 1 Organism: In Vitro
Pathways:Hippo Signaling