serine/threonine protein kinase 3; mammalian STE20-like protein kinase 2; MST-2; STE20-like kinase MST2; serine/threonine protein kinase Krs-1 (STK3, MST2)
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Function
- stress-activated, pro-apoptotic kinase
- following caspase-cleavage, enters the nucleus & induces chromatin condensation followed by internucleosomal DNA fragmentation
- component of the Hippo signaling pathway which plays a role in organ size control & tumor suppression
- phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, & cell migration.
- MST1/MST2 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), & to inhibit tumor formation
- phosphorylates NKX2-1
- inhibited by the C-terminal non-catalytic region
- activated by caspase-cleavage
- full activation also requires homodimerization & autophosphorylation of Thr-180; both are inhibited by the proto-oncogene product RAF1
- interacts with NORE1, which inhibits autoactivation (putative)
- interacts with & stabilizes SAV1
- interacts with RAF1, which prevents dimerization & phosphorylation
- interacts with RASSF1, which leads to enzyme activation
Structure
- homodimerization is mediated via the coiled-coil region
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily
- contains 1 protein kinase domain
- contains 1 SARAH domain
Compartment
Expression
- expressed at high levels in adult kidney, skeletal & placenta tissues
- expressed at very low levels in adult heart, lung & brain