MAPK8IP3
Description
The MAPK8IP3 (mitogen-activated protein kinase 8 interacting protein 3) is a protein-coding gene located on chromosome 16.
C-Jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene. The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. Studies of the similar gene in mouse suggested that this protein may interact with and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. The C. elegans counterpart of this gene is found to regulate synaptic vesicle transport, possibly by integrating JNK signaling and kinesin-1 transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.
== Interactions == MAPK8IP3 has been shown to interact with ASK1, C-Raf, PTK2, MAPK10, Mitogen-activated protein kinase 9, MAPK8, MAP2K1, KLC2, MAP2K7, KLC1, MAPK8IP2 and MAP2K4.
MAPK8IP3, also known as JIP-3 or JNK-interacting protein 3, is a scaffold protein that mediates JNK signaling by bringing together specific components of the MAPK cascade to form a functional JNK signaling module. It may also function as a regulator of vesicle transport, interacting with both JNK signaling components and motor proteins. MAPK8IP3 promotes neuronal axon elongation in a kinesin- and JNK-dependent manner by activating cofilin at axon tips via local activation of JNK, which regulates filopodial dynamics and enhances axon elongation. Its binding to kinesin heavy chains (KHC) promotes kinesin-1 motility along microtubules, essential for axon elongation and regeneration. MAPK8IP3 regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development, acting as an adapter that bridges the interaction between NTRK2/TRKB and KLC1. This drives NTRK2/TRKB axonal, but not dendritic, anterograde transport, crucial for subsequent BDNF-triggered signaling and filopodia formation.
MAPK8IP3 is also known as JIP-3, JIP3, JSAP1, NEDBA, SYD2, syd.
