Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.
Specificity
Natural and recombinant Mouse ALK tyrosine kinase receptor
Subcellular Location
Cell membrane Single-pass type I membrane protein Membrane attachment was crucial for promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP kinase pathway.
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: PHOSPHORYLATION;INTERACTION WITH CBL; IRS1; PIK3R1; PLCG1 AND SHC1;FUNCTION IN PHOSPHORYLATION OF CBL; IRS1 AND SHC1
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: INTERACTION WITH IRS1 AND SHC;PHOSPHORYLATION AT TYR-1096;FUNCTION