Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1, but not isoform 2, activates the JNK MAP kinase pathway through the specific activation of the upstream MKK3 and MKK6 kinases. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of IKKA, and thus NF-kappa-B activation, but not that of JNK. Phosphorylates itself, MBP, activated MAPK8 and tubulins. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization (By similarity). Both isoforms are involved in MAPK14 phosphorylation.
Ubiquitously expressed, with a higher level of expression in testis and brain.
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 protein kinase domain.
Isoforms 1 and 2 are autophosphorylated. C-terminal cleavage of isoform 1 and subsequent nuclear localization requires CASP9 activity. isoform 2 is phosphorylated at 'Ser-1031' by MAPK14. This phosphorylation is required PCDH8 for endocytosis.
Cytoplasmic vesicle membrane. Cytoplasm > cytoskeleton. Nucleus. Catalytically active full-length phosphorylated isoform 1 localizes to microtubules in the cytoplasm predominantly on microtubule cables positioned around the nucleus. A C-terminally truncated form of isoform 1 is present in the nucleus; isoform 2 and kinase-defective, as well as full-length isoform 1 are excluded from the nucleus and Cell projection > dendrite. In dendrites, colocalizes with PCDH8.