Protein adaptor

Adaptor proteins are multi-domain proteins (Fig. 1) that interact with components of signaling pathways [1]. As a consequence of these interactions, adaptor proteins are able to regulate signaling events within the cell, providing spatiotemporal control and specificity, and influencing how a cell responds to a particular stimulus. 

This is perhaps the simplest function provided by adaptor proteins and involves bringing together... 

Adaptor Proteins. Figure 1 Adaptor protein domains. A scheme of the domain structures of some well-characterized adaptor proteins is shown. Descriptions of domain characteristics are in main text except C2, binds to phospholipids GTPase activating protein (GAP) domain, inactivates small GTPases such as Ras Hect domain, enzymatic domain of ubiquitin ligases and GUK domain, guanylate kinase domain. For clarity, not all domains contained within these proteins are shown. 

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

MAP kinase signaling promotes differentiation ofPC12 cells. Adaptor proteins are able to regulate the time course of signaling events, and therefore the cellular outcome. 

In order to bind to target proteins, adaptor proteins contain protein-protein interaction domains which recognize specific target motifs (Fig. 1). Through combinations of these domains, adaptor protein can interact with multiple... 

The interactions between adaptor proteins and their targets are often regulated (see below). By these mechanisms, specific signals are able to control which adaptor proteins, and consequently which target proteins, are recruited to a particular signaling complex. Common methods of adaptor protein regulation are described here. 

Phosphorylation is a common method of regulation. As described above, SH2 domains bind to phosphorylated tyrosine residues. Conversely, phosphorylation of serines and threonines proximal to SH3 and PDZ domains uncouples them from their target motifs. Therefore modulation of protein kinase activity in cells regulates interactions between adaptor proteins and their target proteins. 

Another way in which the function of adaptor proteins is regulated is through modulation of intramolecular interactions. Often one domain will bind to another domain in the same adaptor molecular, preventing... 

At present no compounds targeting adaptor proteins have been approved for clinical use. 

Pawson T (2007) Dynamic control of signaling by modular adaptor proteins. Curr Opin Cell Biol 19 112-116... 

Arrestins act as adaptor proteins that bind to phos-phorylated G protein-coupled receptors (GPCR) and link the receptors to clathrin-coated pits. (3-Arrestins are essential in the internalization of many GPCRs. 

Phospholipid Kinases Ca2+-binding Proteins Adaptor Proteins... 

Adaptor protein, containing one SH2 and two SH3 domains, which assembles signaling complexes at receptors and focal adhesions. 

Motor proteins move along MTs in an ATP-dependent manner. Members of the superfamily of kinesin motors move only to the plus ends and dynein motors only to the minus ends. The respective motor domains are linked via adaptor proteins to their cargoes. The binding activity of the motors to MTs is regulated by kinases and phosphatases. When motors are immobilized at their cargo-binding area, they can move MTs. 

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