CRK-like proto-oncogene, adaptor protein (CRKL)

CRK-like proto-oncogene, adaptor protein (CRKL) is a 39 kDa adaptor protein that consists of one SH2 and two SH3 domains, facilitating the assembly of signal transduction complexes [1, 3]. It is a key component in various signaling pathways, including those initiated by growth factors, cytokines, and integrins, influencing processes like cell adhesion and migration [1, 2]. CRKL is particularly significant in the context of Chronic Myeloid Leukemia (CML), where it serves as the major tyrosine-phosphorylated substrate of the BCR-ABL oncoprotein [3, 4]. The phosphorylation of CRKL by BCR-ABL leads to the activation of downstream pathways such as Ras and PI3K, driving leukemogenesis [4]. Clinically, the ratio of phosphorylated CRKL to total CRKL is a gold-standard biomarker used to assess the degree of BCR-ABL inhibition by tyrosine kinase inhibitors (TKIs) like imatinib and dasatinib [4]. Additionally, CRKL is located within the 22q11.2 chromosomal region, and its hemizygous deletion is linked to the developmental defects seen in DiGeorge syndrome [2, 5]. While direct pharmacological targeting of CRKL is an area of active research, its current clinical significance lies in its role as a central node in oncogenic signaling and a diagnostic indicator of kinase activity [4]. Overexpression of CRKL has also been observed in several solid tumors, including lung and pancreatic cancers, where it contributes to epithelial-mesenchymal transition and metastasis [1, 2].

Other names

Crk-like proteinv-crk avian sarcoma virus CT10 oncogene homolog-likeCRKL

Inhibition of the upstream BCR-ABL tyrosine kinase prevents the phosphorylation of CRKL, thereby disrupting downstream oncogenic signaling pathways such as Ras/MAPK and PI3K/Akt [3, 4].