ALK is the acronym for "Anaplastic Lymphoma Kinase".
The ALK gene is a biologically important protein-coding gene located on chromosome 2p23.2-p23.1. The gene encodes anaplastic lymphoma kinase, a phosphorylase. This enzyme phosphorylates almost exclusively at the first tyrosine of the Y-x-x-Y-Y motif.
ALK acts as a receptor for the ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a pleiotrophin-related factor. Binding of pleiotrophin to ALK leads to activation of the MAPK pathway, which is important for pleiotrophin's anti-apoptotic signaling and regulation of cell proliferation. MDK binding induces phosphorylation of ALK target substrate, insulin receptor (IRS1), activates mitogen-activated protein kinases(MAP kinases) and PI3 kinases, which also leads to induction of cell proliferation. ALK controls NF-kappa-B activation, likely via IRS1 and activation of the serine/threonine kinase AKT. Recruitment of IRS1 to activated ALK and activation of NF-kappa-B are essential for autocrine growth and survival signaling of midkine.