Docking proteins

Abstract

OverviewIn a review on receptor tyrosine kinase (RTK) signalling published a decade ago [1], docking proteins were classified as signal transducers that exhibit a membrane targeting region at the N-terminus, and multiple tyrosine phosphorylation sites that function as binding sites for src homology (SH)2 domains of a variety of downstream effectors. Proteins that fell into this category were members of the growth factor receptor bound (Grb)2-associated binder (Gab) ⁄ Daughter of Sevenless (DOS), insulin receptor substrate (IRS), fibroblast growth factor (FGF) receptor substrate (FRS)2 and downstream of tyrosine kinases (Dok) families. Also, linker for activated T cells (LAT) was classified as a docking protein, although the presence of a transmembrane region raises the issue of whether LAT and other related proteins (e.g. non-T-cell activation linker [2]) should be classified separately. In this context, it is noteworthy that other transmembrane proteins containing tyrosine phosphorylation-dependent recruitment sites (e.g. those with immunoreceptor tyrosine-based activation motifs) are not routinely classified as docking proteins. Another protein that has Keywords Dok; DOS; FRS2; Gab; IRS; protein modules; protein phosphorylation; SH2; signal transduction; tyrosine kinase Docking proteins comprise a distinct category of intracellular, noncatalytic signalling protein, that function downstream of a variety of receptor and receptor-associated tyrosine kinases and regulate diverse physiological and pathological processes. The growth factor receptor bound 2-associated binder ⁄ Daughter of Sevenless, insulin receptor substrate, fibroblast growth factor receptor substrate 2 and downstream of tyrosine kinases protein families fall into this category. This minireview focuses on the structure, function and regulation of these proteins.

Induction of Phagocytosis and Intracellular Signaling by an Inhibitory Channel Catfish Leukocyte Immune-Type Receptor: Evidence for Immunoregulatory Receptor Functional Plasticity in Teleosts

“…ITSM induction of ERK1/2 activation has also been shown to involve recruitment of the cellular phosphatase SHP-2 [58]. SHP-2 recruitment to ITIMs and/or ITSMs causes its specific phosphorylation at a C-terminal tyrosine that serves as a binding site for the SH2-containing adaptor molecule growth factor receptor-bound 2 (Grb2) [59] and this can then promote the activation of the Ras-MEK1/2-ERK1/2 pathway via interactions with members of the Dab/Dos family of scaffolding proteins, known as the Grb2-associated binders (Gab) [60,61,62]. During IpLITR 1.1b-mediated phagocytosis, we predict that Gab2 recruitment to the activated IpLITR 1.1b would likely rely on an indirect mode of interaction.…”

Insulin in the Brain: Sources, Localization and Functions

“…Until now, the IRS family of docking proteins is composed of six proteins named IRS-1 to IRS-6. While IRS-1 to IRS-4 have a C-terminal region capable to recruit specific SH2 domain proteins, IRS-5 and IRS-6 are weakly phosphorylated in response to insulin (reviewed in [90]). Among these family members, IRS-1 and IRS-2 are responsible for most of the pleiotropic effects of insulin and insulin-like growth factor 1 (IGF-1) [91].…”

“…PI3K is mostly believed to be involved in the stimulation of neuronal survival, and the MAPK pathway is mostly involved in cell death [92]. The PI3K pathway is one of the best-characterized signaling pathways activated by the IRS proteins [90] that lead to triggering of both metabolic and growth-promoting functions of insulin and IGF-1 [91]. PI3K activation leads to the formation of phosphatidylinositol-3-4-5-triphosphate and eventually stimulation of phosphoinositide-dependent kinase (PDK-1) activity.…”

Gab2 Phosphorylation by RSK Inhibits Shp2 Recruitment and Cell Motility

“…In addition to SOS, Grb2 associates with a number of docking adapter proteins that modulate RTK signaling (7). Members of the Grb2-associated binder (Gab) family of proteins function downstream of a variety of RTKs and comprise three vertebrate members (Gab1 to Gab3) (8,9).…”