Phospho-MARK1/2/3/4 (Thr215) Antibody - #AF8076

Serine/threonine-protein kinase. Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.

Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation by CaMK1 promotes activity and is required to promote neurite outgrowth. Phosphorylation at Thr-596 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity and promotes binding to 14-3-3 protein YWHAZ, leading to relocation from cell membrane to cytoplasm.

Cell membrane>Peripheral membrane protein. Cytoplasm. Lateral cell membrane. Cytoplasm>Cytoskeleton. Cell projection>Dendrite. Cytoplasm.
Note: Phosphorylation at Thr-596 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm.

High levels of expression in heart, brain, skeletal muscle and pancreas, lower levels observed in lung, liver and kidney.

Homodimer. Interacts with PAK5; leading to inhibit the protein kinase activity (By similarity). Interacts with MAPT/TAU. Interacts with MTCL1 isoform 1; the interaction is direct and increases MARK2 microtubule-binding ability. Interacts (when phosphorylated at Thr-596) with YWHAZ. Interacts with YWHAB, YWHAG and YWHAQ.

(Microbial infection) In case of infection, interacts with H.pylori CagA, leading to inhibit kinase activity and junctional and polarity defects.

The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain.

The KA1 domain mediates binding to phospholipids and targeting to membranes.

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Serine/threonine-protein kinase. Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU. Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1.

Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase activity.

Cell membrane>Peripheral membrane protein. Cell projection>Dendrite. Cytoplasm.

Ubiquitous.

Interacts with MAPT/TAU. Interacts with DLG5 (via coiled-coil domain). Interacts with STK3/MST2 and STK4/MST1 in the presence of DLG5. Interacts with YWHAB, YWHAG, YWHAQ and YWHAZ.

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Serine/threonine-protein kinase. Phosphorylates the microtubule-associated protein MAPT/TAU. Also phosphorylates the microtubule-associated proteins MAP2 and MAP4. Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles. Required for the initiation of axoneme extension during cilium assembly. Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro. Plays a role in cell cycle progression, specifically in the G1/S checkpoint. Reduces neuronal cell survival. Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation.

Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X.

Phosphorylated at Thr-214 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylated throughout the cell cycle.

Cytoplasm>Cytoskeleton>Microtubule organizing center>Centrosome. Cytoplasm>Cytoskeleton>Microtubule organizing center. Cytoplasm>Cytoskeleton>Cilium basal body. Cytoplasm>Cytoskeleton>Cilium axoneme. Cytoplasm. Cell projection>Dendrite.
Note: Localized at the tips of neurite-like processes in differentiated neuroblast cells. Detected in the cytoplasm and neuropil of the hippocampus.

Ubiquitous. Isoform 2 is brain-specific. Expressed at highest levels in brain and testis. Also expressed in heart, lung, liver, muscle, kidney and spleen.

Interacts with MAPT/TAU. Interacts with gamma-tubulin. Interacts with ODF2. Interacts with USP9X. Interacts with YWHAQ.

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.