CBL Protein, Human (GST)

CBL is an E3 ubiquitin-protein ligase that acts as a negative regulator of multiple signaling pathways by mediating ubiquitination of cell surface receptors. It accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and transfers it to substrates, promoting their degradation via the proteasome. CBL recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8, and KDR, and mediates their ubiquitination to terminate signaling. It also targets membrane-bound HCK, SRC, and other SRC family kinases for ubiquitination and degradation. Additionally, CBL ubiquitinates EGFR and SPRY2, and following interaction between NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, it ubiquitinates NECTIN1, leading to its removal from the cell surface. CBL participates in hematopoietic cell signaling, plays a key role in osteoblast differentiation and apoptosis regulation, and is essential for osteoclastic bone resorption. Its Tyr-731 phosphorylated form activates and recruits phosphatidylinositol 3-kinase to the cell membrane in a critical signaling pathway. CBL may functionally couple with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, it is required for feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling via ubiquitination and internalization of PDGFRA (by similar).