STK3
STK3 (serine/threonine kinase 3, also known as MST2 and KRS1) is a stress-activated, pro-apoptotic serine/threonine kinase of the STE20 subfamily. It is a core component of the Hippo signalling pathway, where it restricts proliferation and promotes apoptosis. Browse Assay Genie's current range of STK3 research reagents below, or read on for the biology behind the target.
STK3 is a serine/threonine kinase that acts as a growth suppressor. In the Hippo pathway, STK3 and its paralogue STK4 (MST1), in complex with the regulatory protein SAV1, phosphorylate and activate LATS1/2 in complex with MOB1. LATS kinases in turn phosphorylate and inactivate the YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus, where it would otherwise regulate genes important for cell proliferation, cell death and cell migration. STK3 and STK4 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells) and to inhibit tumour formation.
STK3 also has roles beyond the core cascade. It phosphorylates NKX2-1, MOBKL1A and RASSF2, and phosphorylates MOBKL1B on Thr-74, acting cooperatively with MOBKL1B to activate STK38. It phosphorylates NEK2 and contributes to centrosome disjunction by regulating NEK2 localisation to the centrosome and its ability to phosphorylate CROCC and CEP250. With SAV1, it activates the transcriptional activity of ESR1 by modulating its phosphorylation, and it positively regulates RAF1 activation by suppressing the inhibitory phosphorylation of RAF1 on Ser-259.
The STK3 protein is activated by proapoptotic molecules. Caspase cleavage removes the inhibitory C-terminal portion, and the N-terminal fragment is transported to the nucleus, where it homodimerises to form the active kinase. There it induces chromatin condensation followed by internucleosomal DNA fragmentation during apoptosis. The STK3 gene produces multiple transcript variants encoding different isoforms. STK3 belongs to the STK3/STK4 kinase family within the STE Ser/Thr protein kinase family, and was previously named serine/threonine kinase 3 (Ste20, yeast homolog).
STK3 and STK4 with SAV1 activate LATS1/2 and MOB1, leading to inactivation of YAP1 and WWTR1/TAZ.
Following caspase cleavage, STK3 enters the nucleus and induces chromatin condensation and internucleosomal DNA fragmentation.
STK3 helps restrict proliferation, control organ size and inhibit tumour formation, including repression of hepatocyte proliferation in the liver.
STK3 phosphorylates NEK2 to influence centrosome disjunction, and regulates RAF1, ESR1 and STK38 activity.
STK3 is a stress-activated, pro-apoptotic kinase and a core Hippo pathway component. With SAV1 it activates LATS1/2, which inactivate YAP1 and WWTR1/TAZ, restricting proliferation and promoting apoptosis. After caspase cleavage it also enters the nucleus and induces chromatin condensation.
STK3 is also known as MST2 and KRS1, and was formerly named serine/threonine kinase 3 (Ste20, yeast homolog). Its UniProt name is serine/threonine-protein kinase 3. The gene produces multiple transcript variants that encode different isoforms.
STK3 has a mouse ortholog, Stk3, and a rat ortholog listed as Stk24. It belongs to the STE20 subfamily and the STK3/STK4 kinase family, with STK4 (MST1) as its close partner in Hippo signalling. Check the datasheet of any product for its validated reactivity.
Other serine/threonine kinases, including the STK3 paralogue STK4 and further STE20-related kinases, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13188; product specifications from Assay Genie datasheets.