background:
MAP4K6 is a serine/threonine kinase belonging to the germinal center kinase (GCK) family. These kinases regulate a wide variety of cellular processes by coupling cell surface receptors to MAPK pathways. This kinase appears to act upstream of the JUN N-terminal pathway and may be involved in brain development. It may also play a role in the response to environmental stress, in cytoskeleton reorganization, cell adhesion, and cell motility. Alternative splicing occurs at this locus and four transcript variants encoding distinct isoforms have been identified.
Function:
Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1.
Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration.
Subunit:
Interacts with TANC1. Interacts with RAP2A. Isoform 4 interacts with NCK1.
Subcellular Location:
Cytoplasm. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Cell projection, axon. Cell projection, dendrite.
Isoform 4: Golgi apparatus.
Tissue Specificity:
Expressed in the brain, isoform 2 is more abundant than isoform 1. Isoform 3 is ubiquitously expressed. Isoform 1 is most abundant in the skeletal muscle. Isoform 4 is ubiquitously expressed with relative high levels in brain, skeletal muscle, pancreas and testis.
Post-translational modifications:
Autophosphorylated.
Similarity:
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Contains 1 CNH domain.
Contains 1 protein kinase domain.
Database links:
UniProtKB/Swiss-Prot: Q8N4C8.2
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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