TAOK2

TAOK2 is a serine/threonine protein kinase that is involved in many different processes, including, cell signaling, microtubule organization and stability, and apoptosis.

Full Name

TAO kinase 2

Function

Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. 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 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. 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. Both isoforms are involved in MAPK14 phosphorylation.

Biological Process

Biological Process actin cytoskeleton organizationIDA:UniProtKB1 Publication
Biological Process activation of protein kinase activityTAS:ARUK-UCL1 Publication
Biological Process apoptotic processNAS:UniProtKB1 Publication
Biological Process axonogenesisIGI:ARUK-UCL1 Publication
Biological Process basal dendrite arborizationISS:ARUK-UCLBy Similarity
Biological Process basal dendrite morphogenesisISS:ARUK-UCLBy Similarity
Biological Process cell migrationNAS:UniProtKB1 Publication
Biological Process cellular response to DNA damage stimulusIDA:UniProtKB1 Publication
Biological Process focal adhesion assemblyIDA:UniProtKB1 Publication
Biological Process intracellular signal transductionIBA:GO_Central1 Publication
Biological Process MAPK cascadeIBA:GO_Central1 Publication
Biological Process mitotic G2 DNA damage checkpoint signalingIMP:UniProtKB1 Publication
Biological Process neuron projection morphogenesisIBA:GO_Central1 Publication
Biological Process positive regulation of JNK cascadeIDA:UniProtKB1 Publication
Biological Process positive regulation of MAPK cascadeIDA:UniProtKB1 Publication
Biological Process positive regulation of protein autophosphorylationTAS:ARUK-UCL1 Publication
Biological Process positive regulation of stress-activated MAPK cascadeIMP:UniProtKB1 Publication
Biological Process protein autophosphorylationTAS:ARUK-UCL1 Publication
Biological Process protein phosphorylationIBA:GO_Central1 Publication
Biological Process protein targeting to membraneNAS:UniProtKB1 Publication
Biological Process regulation of actin cytoskeleton organizationISS:ARUK-UCLBy Similarity
Biological Process regulation of cell growthNAS:UniProtKB1 Publication
Biological Process regulation of cell shapeIDA:UniProtKB1 Publication
Biological Process regulation of MAPK cascadeIBA:GO_Central1 Publication
Biological Process stress-activated MAPK cascadeIDA:UniProtKB1 Publication

Cellular Location

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.
Isoform 2
Cell projection, dendrite
In dendrites, colocalizes with PCDH8.

PTM

Isoforms 1 and 2 are autophosphorylated.
C-terminal cleavage of isoform 1 and subsequent nuclear localization requires CASP9 activity.
Autophosphorylated. Phosphorylated by ATM.
Isoform 2
Phosphorylated on Ser-1031 by MAPK14. This phosphorylation is required PCDH8 for endocytosis (By similarity).