Abelson tyrosine-protein kinase 2 (ABL2)

Abelson tyrosine-protein kinase 2 (ABL2), frequently referred to as ARG (Abelson-related gene), is a non-receptor tyrosine kinase that serves as a critical link between extracellular stimuli and the regulation of the actin cytoskeleton [1, 14]. It is a member of the Abelson family, sharing significant structural homology with ABL1, including SH3, SH2, and catalytic kinase domains; however, ABL2 is uniquely characterized by its C-terminal domains that allow direct binding to F-actin and microtubules, enabling it to modulate cytoskeletal stability and morphogenesis [2, 11]. In normal physiology, ABL2 mediates processes such as cell motility, adhesion, and axon guidance [1, 9]. In pathological contexts, ABL2 is recognized as a proto-oncogene that can be activated via chromosomal translocations (such as the ETV6-ABL2 fusion in leukemias), gene amplification, or protein overexpression in solid tumors like lung and hepatocellular carcinoma [4, 6, 8, 13]. Because of its high structural similarity to ABL1, it is a primary or secondary target of multi-kinase inhibitors such as imatinib and dasatinib, which are used to treat Philadelphia chromosome-positive malignancies [3, 7, 10, 14]. Beyond oncology, research is increasingly exploring ABL2's involvement in the pathology of neurodegenerative diseases and its exploitation by pathogens during infection [7, 9, 14].

Other names

ARGAbelson-related geneABLLABL proto-oncogene 2, non-receptor tyrosine kinaseTyrosine-protein kinase ARGAbelson murine leukemia viral oncogene homolog 2c-abl oncogene 2

ATP-competitive inhibition of the tyrosine kinase domain enzymatic activity