ALK and LTK ligand 2 (ALKAL2)

ALK and LTK ligand 2 (ALKAL2), also known as Augmentor alpha and FAM150B, is a secreted cytokine that functions as a high-affinity ligand for the receptor tyrosine kinases ALK and LTK[1][2][3]. By binding to the extracellular domain of these receptors—particularly ALK—ALKAL2 robustly activates their intracellular kinase domains, driving downstream signal transduction pathways associated with cell growth and proliferation. ALKAL2 is expressed in tissues such as the adrenal gland and is especially relevant in the context of neuroblastoma, a cancer where ALK activation can occur both via mutations and ligand-induced signaling[1][3]. Experimental evidence confirms that ALKAL2 can "superactivate" mutant forms of ALK commonly found in neuroblastoma, suggesting possible roles in disease etiology and therapeutic response[1][3]. The ability of ALKAL2 to activate ALK and LTK positions both the ligand and its receptors as potential therapeutic targets in oncology. - ALKAL2 activates ALK and LTK by binding their glycine-rich extracellular domains and triggering receptor phosphorylation. - The ligand’s effect can be blocked by ALK inhibitors such as crizotinib, which demonstrate clinical efficacy in tumors with ALK pathway activation[1][2]. - ALKAL2 and its homolog FAM150A (Augmentor beta) define a new family of RTK ligands, showing no significant homology to other protein families and potentially serving distinct signaling roles[3].

Other names

ALKAL2Augmentor alpha (AUG-α)FAM150BPRO1097RGPG542UNQ542/PRO1097AUGAaugmentor alphaaugmentor-betafamily with sequence similarity 150 member Bprotein FAM150B

Most drugs interact with ALKAL2 indirectly, inhibiting the downstream receptor (ALK) that is activated by ALKAL2[1][2]. - Example: Crizotinib competitively inhibits ALK's kinase domain, blocking signaling initiated by ALKAL2[1][2].