growth factor receptor-bound protein-2 (grb2) or ASH protein

Function

• adapter protein that provides a critical link between cell surface growth factor receptors & Ras signaling
• serves as adapter protein for Sos (ras guanine nucleotide exchange factor)
• binds to Y925 within FAT domain of focal adhesion kinase (FAK) & to Y? of src via SH2 domain & to mSos via SH3 domain
• isoform GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element
• isoform GRB3-3 acts as a dominant negative protein over GRB2 & by suppressing proliferative signals, may trigger active programmed cell death
• associates with activated Tyr-phosphorylated EGF receptors & PDGF receptors via its SH2 domain
• associates with other cellular Tyr-phosphorylated proteins including as SIT1, IRS1, SHC & LNK; probably via concerted action of both its SH2 & SH3 domains
• seems to interact with RAS in the signaling pathway leading to DNA synthesis
• binds to & translocates guanine-nucleotide exchange factors SOS
• interacts with phosphorylated TOM1L1 & MET
• interacts with the phosphorylated C-terminus of SH2B2
• interacts with phosphorylated SIT1, LAX1, LAT, LAT2 & LIME1 upon TCR &/or BCR activation
• interacts with PTPNS1, REPS2 & the syntrophin SNTA1
• interacts with REPS1 & PIK3C2B via its SH3 domains (putative)
• interacts with HCV NS5A via its SH3 domains
• interacts with CBL & CBLB
• interacts with SHB, INPP5D/SHIP1, SKAP1 & SKAP2

Structure

• Sem-5 (C. elegans) homolog
• belongs to the GRB2/sem-5/DRK family
• contains 1 SH2 domain
• contains 2 SH3 domains
• SH3 domains mediate interaction with SHB

Alternative splicing

named isoforms=2

More general terms

• growth factor receptor-bound protein (GRB GRB adapter protein)

Additional terms

• ras signal transduction

Component of

• grb2/sos complex

Database

• UniProt: http://www.uniprot.org/uniprot/P62993.html
• OMIM: https://mirror.omim.org/entry/108355