STK4
Description
The STK4 (serine/threonine kinase 4) is a protein-coding gene located on chromosome 20.
Serine/threonine-protein kinase 4 is an enzyme that in humans is encoded by the STK4 gene.
== Function == The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p (sterile 20 protein) kinase, which acts upstream of the stress-induced mitogen-activated protein kinase (MAPK) cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it‘s possible that this protein induces the chromatin condensation observed in this process.
== Interactions == STK4 has been shown to interact with PRKRIR. STK4 has also been shown to prevent, through Yap1 coactivator modulation, haematological tumor cell apoptosis.
STK4 is a stress-activated, pro-apoptotic kinase. Following caspase-cleavage, it translocates to the nucleus, where it induces chromatin condensation and internucleosomal DNA fragmentation. It is a crucial component of the Hippo signaling pathway, which plays a key role in regulating organ size and suppressing tumor growth by limiting cell proliferation and promoting apoptosis. STK4, in complex with its regulatory protein SAV1, activates LATS1/2 in conjunction with its regulatory protein MOB1. This cascade ultimately phosphorylates and inactivates the YAP1 oncoprotein, preventing its nuclear translocation and hindering the regulation of cellular genes involved in cell proliferation, death, and migration. STK4 also plays a role in inhibiting the proliferation of mature hepatocytes, preventing the activation of facultative adult liver stem cells (oval cells), and suppressing tumor formation. Additionally, STK4 phosphorylates histone H2B (H2BS14ph) during apoptosis, FOXO3 upon oxidative stress, triggering its nuclear translocation and cell death, MOBKL1A, MOBKL1B, and RASSF2. It also alters the binding affinity of TNNI3 (cardiac Tn-I) to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T) by phosphorylation. Furthermore, STK4 phosphorylates FOXO1 on ‘Ser-212‘, regulating its activation and stimulating PMAIP1 transcription in a FOXO1-dependent manner. It also phosphorylates SIRT1, inhibiting its deacetylation of p53/TP53, which promotes p53/TP53-dependent transcription and apoptosis in response to DNA damage. STK4 acts as an inhibitor of PKB/AKT1 and phosphorylates AR on ‘Ser-650‘, suppressing its activity by interfering with PKB/AKT1 signaling and hindering the formation of AR-chromatin complexes.
STK4 is also known as KRS2, MST1, YSK3.
