CrkL

Crk-like (CrkL) is an adaptor protein encoded by the human CRKL gene and is a member of the Crk family. It has the canonical domain architecture of Crk family adaptors, with an SH2 domain flanked by two SH3 domains, enabling simultaneous binding to phosphotyrosine-containing motifs and proline-rich regions.

CrkL participates in signaling pathways downstream of various receptor and non-receptor tyrosine kinases, linking activated receptors to downstream effectors such as SOS and DOCK1. Through these interactions, CrkL influences processes including Ras–MAPK signaling, actin cytoskeleton remodeling, cell adhesion, and cell migration. Its binding partners include proteins like p130Cas/BCAR1 and paxillin, among others, which helps coordinate signals from growth factors and integrins to cytoskeletal and transcriptional responses.

Biological roles of CrkL are broad and include important functions in development. In mice, CRKL is essential for normal neural crest-derived and cardiovascular development, and genetic disruption can lead to congenital defects. In hematopoietic and signaling contexts, CrkL participates in pathways that regulate cell growth and organization.

Clinical significance centers on CrkL as a substrate of the BCR-ABL oncoprotein. Phosphorylated CrkL serves as a diagnostic and monitoring biomarker in BCR-ABL1-positive leukemias, such as chronic myeloid leukemia and Philadelphia chromosome–positive ALL, reflecting ongoing tyrosine kinase activity and treatment response. Altered CRKL expression or regulation has also been observed in various cancers and may contribute to oncogenic signaling in some contexts.