CRK-like adaptor protein (CRKL) (CRKL)

CRK-like adaptor protein (CRKL) is a pivotal signaling scaffold consisting of one SH2 and two SH3 domains that mediates protein-protein interactions in various intracellular pathways [1, 2]. It plays a critical role in hematopoiesis and is the primary substrate for the BCR-ABL oncoprotein in chronic myeloid leukemia (CML) [1, 3]. In CML cells, CRKL is constitutively phosphorylated, leading to the activation of downstream pathways such as Ras/MAPK and PI3K/Akt, which drive uncontrolled cell proliferation and survival [3, 5]. Beyond leukemia, CRKL is overexpressed in several solid tumors, including lung and pancreatic cancers, where it promotes epithelial-mesenchymal transition and metastasis [5, 6]. It is also a key gene involved in the pathogenesis of DiGeorge syndrome due to its location on chromosome 22q11.2 and its role in pharyngeal arch development [4]. While not typically the primary target of small molecule inhibitors, CRKL serves as the gold-standard biomarker for assessing the efficacy of BCR-ABL tyrosine kinase inhibitors (TKIs) like imatinib [3, 6]. Emerging therapeutic strategies are exploring the direct disruption of CRKL SH2 or SH3 domain interactions to overcome resistance to conventional kinase inhibitors [6].

Other names

CrkLCrk-like proteinv-crk avian sarcoma virus CT10 oncogene homolog-like

Inhibition of upstream BCR-ABL tyrosine kinase activity to prevent CRKL phosphorylation and downstream signaling; experimental disruption of SH2/SH3 domain-mediated protein-protein interactions.