ALK Protein, Mouse (HEK293, hFc)

ALK is a neuronal receptor tyrosine kinase primarily and transiently expressed in specific regions of the central and peripheral nervous systems, playing a crucial role in nervous system genesis and differentiation. It also functions as a key thinness protein involved in resistance to weight gain by regulating energy expenditure in hypothalamic neurons, acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis. Upon activation by the ALKAL2 ligand at the cell surface, ALK transduces extracellular signals into intracellular responses. Ligand binding to its extracellular domain induces tyrosine kinase activation, triggering the mitogen-activated protein kinase (MAPK) pathway. It phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif and induces tyrosine phosphorylation of CBL, FRS2, IRS1, SHC1, and MAP kinases MAPK1/ERK2 and MAPK3/ERK1. ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK): PTN binding activates the MAPK pathway, supporting anti-apoptotic signaling and cell proliferation regulation, while MDK binding induces phosphorylation of IRS1, activates MAPKs and PI3-kinase, and promotes cell proliferation. Additionally, ALK drives NF-kappa-B activation, likely through IRS1 and AKT serine/threonine kinase (by similar).