GRB2
GRB2 (growth factor receptor bound protein 2, also known as NCKAP2) is an adaptor protein built from one SH2 domain and two SH3 domains. It links tyrosine-phosphorylated proteins to proline-rich binding partners in signal transduction pathways downstream of growth factor receptors. Browse Assay Genie's current range of GRB2 research reagents below, or read on for the biology behind the target.
GRB2 functions as an adaptor rather than an enzyme. The protein encoded by the GRB2 gene binds the epidermal growth factor receptor (EGFR) and contains one SH2 domain and two SH3 domains. The SH2 domain recognises tyrosine-phosphorylated sequences, while the two SH3 domains direct complex formation with proline-rich regions of other proteins. This arrangement lets GRB2 couple activated receptors to downstream signalling components.
GRB2 belongs to the GRB2/sem-5/DRK family and is classified by HGNC within the SH2 domain containing, SH3 domain containing and growth factor receptor bound protein 2 gene groups. UniProt records the protein in the nucleus, cytoplasm, endosome and Golgi apparatus. The gene is similar to the Sem5 gene of C. elegans, which is involved in a signal transduction pathway, and orthologues are annotated in both mouse and rat (Grb2). Two alternatively spliced transcript variants encoding different isoforms have been reported for this gene.
The UniProt function annotation describes a form of the protein that behaves differently from the canonical adaptor. It does not bind phosphorylated EGFR, yet it inhibits EGF-induced transactivation of a RAS-responsive element. It is described as acting as a dominant negative over GRB2: by suppressing proliferative signals it may trigger active programmed cell death. Mechanistically, it inhibits RAS-ERK signalling and downstream cell proliferation by competing with GRB2 for SOS1 binding, thereby regulating SOS1 membrane recruitment. These observations make GRB2 and its variants a useful focus for studies of how receptor signals are routed to RAS-ERK signalling.
GRB2 binds EGFR and uses its SH2 domain to recognise tyrosine-phosphorylated sequences, making it a core component for studying receptor signal transduction.
A GRB2 variant competes with GRB2 for SOS1 binding and inhibits RAS-ERK signalling, so the protein is relevant to studies of SOS1 membrane recruitment.
Its SH2 and two SH3 domains mediate complex formation with phosphotyrosine and proline-rich motifs, supporting work on adaptor-based protein assemblies.
Dominant negative activity over GRB2 suppresses proliferative signals and may trigger programmed cell death, linking the protein to growth control research.
GRB2 is an adaptor protein with one SH2 domain and two SH3 domains. The SH2 domain binds tyrosine-phosphorylated sequences, and the SH3 domains bind proline-rich regions of other proteins. In this way it links activated receptors such as EGFR to downstream signalling complexes.
HGNC lists NCKAP2 as an alias, and the protein is also called growth factor receptor-bound protein 2. NCBI Gene reports two alternatively spliced transcript variants encoding different isoforms. UniProt describes one form that acts as a dominant negative over GRB2 and does not bind phosphorylated EGFR.
Yes. Mouse and rat both carry a Grb2 orthologue, and the gene is similar to the Sem5 gene of C. elegans, which is involved in signal transduction. The protein belongs to the GRB2/sem-5/DRK family. Check the datasheet of any product for its validated reactivity.
Other GRB family adaptors and signalling partners of GRB2 in the EGFR, SOS1 and RAS-ERK pathway.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P62993; product specifications from Assay Genie datasheets.