Anaplastic lymphoma kinase (ALK)

Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase in the insulin receptor superfamily, is predominantly expressed in the brain and implicated in neuronal development and cognition. ALK catalyzes the transference of a gamma-phosphate group from adenosine triphosphate (ATP) to a tyrosine residue on a substrate protein. Therefore, it catalyzes a tyrosine residue phosphorylation reaction on its substrate proteins. The phosphorylation and dephosphorylation of proteins are critical reactions catalyzed by different enzymes (kinases and phosphatases), which play critical roles in various cellular functions.

ALK gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression. ALK is a transmembrane tyrosine kinase receptor that, upon ligand binding to its extracellular domain, undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. When activated in cancer it represents a target for specific inhibitors, such as Crizotinib, Ceritinib, Alectinib etc. which use has demonstrated significant effectiveness in ALK-positive non-small cell lung cancer particularly.