ALK and LTK ligand 1 (ALKAL1)

ALK and LTK ligand 1 (ALKAL1, also called FAM150A/augmentor beta) is a secreted cytokine-like protein that serves as a physiological ligand for the receptor tyrosine kinases LTK and, to a lesser extent, ALK. Its binding induces receptor dimerization, phosphorylation, and activation of downstream signal transduction pathways such as ERK1/2. ALKAL1’s activation of LTK is potent, while its stimulation of ALK is comparatively weak. Aberrant signaling through ALK and LTK, sometimes driven by overexpression or mutation (especially in cancers like neuroblastoma), makes their pathways attractive therapeutic targets. ALKAL1, along with its paralog ALKAL2 (FAM150B, augmentor alpha), helps regulate these signaling events in normal and disease states.

Other names

FAM150Aaugmentor betaAUG-betaAUGBAugmentor-betaUNQ9433/PRO34745family with sequence similarity 150 member Aprotein FAM150A

ALKAL1 binds to the extracellular domain of LTK (and weakly, ALK), stimulating receptor phosphorylation and downstream activation of ERK1/2 MAPK signaling. Crizotinib inhibits ALK and LTK activation by competing with ATP in their kinase domains.