The adaptor protein acts primarily as a flexible molecular scaffold that mediates protein-protein and protein-lipid interactions in signal transduction pathways. The specificity of signaling can be determined by the type of protein binding module encoded by the adaptor protein, the sequence of these domains or motifs determining the specificity of binding, as well as the proximity of subcellular localization and binding partners. Thus, localization of adaptor proteins modulates cellular signaling in a spatial and temporal manner. Adaptor proteins typically contain several domains in their structure that allow recognition of specific amino acid sequences within proteins containing phosphotyrosine residues, and SH3 domains, which recognize proteins, with several other specific proteins, for example, the SH2 domain. A proline-rich sequence within the context of a particular peptide sequence. Lipid interaction modules such as PH (pleckstrin homology) or PX (phox homology) domains bind to phosphatidylinositol and determine the location of the adaptor protein. In this way, adaptor proteins can amplify receptor-mediated signals and facilitate the coupling of signals to different signal transduction pathways.
Signal transduction adapter protein
Signal transduction adapter protein (STAP) is a protein that helps the major proteins in very signal transduction pathways. The adapter protein contains various protein binding modules that link the protein binding ligands together to facilitate the production of larger signal complexes. These proteins themselves often lack any intrinsic enzymatic activity, rather than mediating specific protein-protein interactions that promote protein complex formation. Examples of adapter proteins include MYD88, Grb2 and SHC1. The adapter protein typically contains several domains in its structure, allowing specific phase-specific SH2 domains to recognize specific amino acid sequences in proteins containing phosphotyrosine residues, and the SH3 domain is specific for proteins. The proline-rich sequence is recognized in the context of the peptide sequence. Many other types of interaction domains have been observed in adapters and other signaling proteins that allow for a rich variety of specific and coordinated protein-protein interactions within the cell during signal transduction. Many of the specificities of signal transduction rely on the recruitment of many signal components into short-lived active complexes in response to activation signals.
In their pure form, the adaptor protein lacks any intrinsic enzymatic activity and serves as an intracellular platform for amplification and coordination assembly of multimeric protein complexes.
Adapter proteins provide a diverse array of functions, including:
1.Co-localize signaling proteins in a specific area of the cell
2.Bring together enzymes and substrates to facilitate specific reactions
3.Coordinate diverse signals in a timely fashion
A common feature of adaptor proteins is the organization of modular structures; a limited number of highly evolved conserved protein sequences ("domains" or "modules") are combined to produce a variety of protein structures with specific cellular functions and multiple connectivity capabilities.
Genes encoding adaptor proteins include:
Breast cancer anti-estrogen resistance protein 3 is a protein encoded by the BCAR3 gene in humans. Breast tumors initially depend on the growth and progression of estrogen and can be inhibited by anti-estrogens such as tamoxifen. However, breast cancer progresses to become anti-estrogen resistant. The breast cancer anti-estrogen resistance gene 3 was identified in a search for genes involved in the development of estrogen resistance. This gene encodes a component of intracellular signal transduction that elicits estrogen-independent proliferation in human breast cancer cells. The protein contains a putative src homology 2 (SH2) domain and is a hallmark of a cellular tyrosine kinase signaling molecule that is partially homologous to the cell division cycle protein CDC48.
The Grb2-related adaptor protein is a protein encoded by the GRAP gene in humans. This gene encodes a member of the Grb2/Sem5 (C. elegans homolog) / Drk (Drosophila homolog) family. This member functions as a cytoplasmic signaling protein containing an SH2 domain flanked by two SH3 domains. The SH2 domain interacts with stem cell factors and ligand-activated receptors of erythropoietin and promotes the formation of stable complexes with BCR-ABL oncoproteins. The protein also binds to the Ras guanine nucleotide exchange factor SOS1 (a sub-seven homolog 1) via its N-terminal SH3 domain.
GRB2-related adaptor 2 (also known as the GRB2-associated adaptor downstream of Shc (GADS)) is a 37 kDa protein that is encoded by the GRAP2 gene in humans. This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its associated family member GRB2-associated adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins via its SH3 domain, such as GRB2-associated binding protein 1 (GAB1) and SLP-76 leukocyte protein (LCP2). There are transcript variants that utilize alternative polyA sites.
1. Pawson T.; et al. Dynamic control of signaling by modular proteins. Curr Opin Cell Biol, 2007, 19(2):112–116
2. Pawson T.; et al. Assembly of cell regulatory systems through protein interaction domains. Science, 2007, 300(5618):445–452.