ALK tyrosine kinase receptor (also known as anaplastic lymphoma kinase, ALK) is a 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 [].ALK transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. 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 [, , ]. ALK 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 [].
