background:
STK3 is a stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation.
Function:
Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.
Subunit:
Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B and STK38. Interacts with RASSF2 (via SARAH domain).
Subcellular Location:
Cytoplasm. Nucleus. Membrane. The truncated form (MST3/N) translocates to the nucleus. Co-localizes with STK38L in the membrane.
Post-translational modifications:
Proteolytically processed by caspases during apoptosis. Proteolytic cleavage results in kinase activation, nuclear translocation of the truncated form (MST3/N) and the induction of apoptosis.
Isoform B is activated by phosphorylation by PKA. Oxidative stress induces phosphorylation. Activated by autophosphorylation at Thr-190 and phosphorylation at this site is essential for its function. Manganese, magnesium and cobalt-dependent autophosphorylation is mainly on threonine residues while zinc-dependent autophosphorylation is on both serine and threonine residues.
Similarity:
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Contains 1 protein kinase domain.
Database links:
Entrez Gene: 532455 Cow
Entrez Gene: 8428 Human
Entrez Gene: 223255 Mouse
Entrez Gene: 361092 Rat
Omim: 604984 Human
SwissProt: Q9Y6E0 Human
SwissProt: Q99KH8 Mouse
SwissProt: B0LT89 Rat
Unigene: 508514 Human
Unigene: 390756 Mouse
Unigene: 442081 Mouse
Unigene: 472866 Mouse
Unigene: 105397 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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