Growth factor receptor-bound protein 2

Growth factor receptor-bound protein 2 (GRB2) is a non-enzymatic adapter protein that orchestrates signaling cascades from cell surface receptors to downstream cellular responses including gene expression, immunity regulation, autophagy, DNA repair, and cell death pathways (UniProt: P62993). It plays a critical role in T-cell activation by linking phosphorylated LAT to the SOS1–KRAS–RAF1–MAPK axis, and similarly amplifies B-cell signaling through ERK activation. GRB2 also regulates the autophagy-versus-necroptosis balance upstream of EGFR, controls miRNA biogenesis, and protects stalled replication forks during DNA damage responses.

In Alzheimer's disease, GRB2 shows elevated abundance in post-mortem AD brain tissue relative to age-matched controls. Chaparral AD proteomics data from TMT-labeled human brain fractions (P2, P3, S2, S3) detected a mean log2 fold-change of +0.10, indicating modest upregulation across the assayed subcellular fractions. This increased expression may reflect dysregulation of immune signaling, growth factor receptor pathways, or stress responses characteristic of AD neuropathology, though the precise functional consequences of GRB2 elevation in AD brain remain to be elucidated.