Recombinant Human GRB2 protein

Specifications

Form

Lyophilized

General info

Function

Non-enzymatic adapter protein that plays a pivotal role in precisely regulated signaling cascades from cell surface receptors to cellular responses, including signaling transduction and gene expression (PubMed : 11726515, PubMed : 37626338). Thus, participates in many biological processes including regulation of innate and adaptive immunity, autophagy, DNA repair or necroptosis (PubMed : 35831301, PubMed : 37626338, PubMed : 38182563). Controls signaling complexes at the T-cell antigen receptor to facilitate the activation, differentiation, and function of T-cells (PubMed : 36864087, PubMed : 9489702). Mechanistically, engagement of the TCR leads to phosphorylation of the adapter protein LAT, which serves as docking site for GRB2 (PubMed : 9489702). In turn, GRB2 establishes a a connection with SOS1 that acts as a guanine nucleotide exchange factor and serves as a critical regulator of KRAS/RAF1 leading to MAPKs translocation to the nucleus and activation (PubMed : 12171928, PubMed : 25870599). Functions also a role in B-cell activation by amplifying Ca(2+) mobilization and activation of the ERK MAP kinase pathway upon recruitment to the phosphorylated B-cell antigen receptor (BCR) (PubMed : 25413232, PubMed : 29523808). Plays a role in switching between autophagy and programmed necrosis upstream of EGFR by interacting with components of necrosomes including RIPK1 and with autophagy regulators SQSTM1 and BECN1 (PubMed : 35831301, PubMed : 38182563). Regulates miRNA biogenesis by forming a functional ternary complex with AGO2 and DICER1 (PubMed : 37328606). Functions in the replication stress response by protecting DNA at stalled replication forks from MRE11-mediated degradation. Mechanistically, inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks (PubMed : 38459011). Additionally, directly recruits and later releases MRE11 at DNA damage sites during the homology-directed repair (HDR) process (PubMed : 34348893).. Isoform 2. Does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. Mechanistically, inhibits RAS-ERK signaling and downstream cell proliferation by competing with GRB2 for SOS1 binding and thus by regulating SOS1 membrane recruitment (PubMed : 36171279).

Sequence similarities

Belongs to the GRB2/sem-5/DRK family.

Post-translational modifications

Phosphorylation of Tyr-209 in the C-terminal SH3 domain reduces its binding to SOS1.. Ubiquitinated by RNF173, leading to proteasomal degradation and inhibition of the RAF/MEK/ERK pathway (PubMed:37328606). In the nucleus, polyubiquitinated by RBBP6 at Lys-109 at DNA damage sites (PubMed:34348893).

Subcellular localisation

Nucleus