CBLB/RNF56 Protein, Human (HEK293, His)

CBLB/RNF56 Protein serves as an E3 ubiquitin-protein ligase, mediating the transfer of ubiquitin from specific E2 ubiquitin-conjugating enzymes to substrates, ultimately promoting their degradation by the proteasome. It plays a pivotal role in negatively regulating signal transduction pathways initiated by TCR, BCR, and FCER1. In naive T-cells, CBLB inhibits VAV1 activation upon TCR engagement and mandates CD28 costimulation for proliferation and IL-2 production. Furthermore, it promotes ubiquitination of PIK3R1/p85, hindering its recruitment to the TCR and subsequent activation. In activated T-cells, CBLB hampers PLCG1 activation and calcium mobilization upon restimulation, contributing to the induction of anergy. In B-cells, it ubiquitinates SYK, facilitating its proteasomal degradation. Additionally, CBLB may play a role in SRC ubiquitination and could be involved in EGFR ubiquitination and internalization. It is suggested to work in conjunction with the E2 ubiquitin-protein ligase UB2D3 and, when associated with CBL, is essential for the proper feedback inhibition of ciliary PDGFRA signaling through ubiquitination and internalization of PDGFRA.