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Signal transducing adaptor proteins (STAPs) are proteins that are accessory to main proteins in a signal transduction pathway.Adaptor proteins contain a variety of protein-binding modules that link protein-binding partners together and facilitate the creation of larger signaling complexes. These proteins tend to lack any intrinsic enzymatic activity themselves, instead mediating specific protein–protein interactions that drive the formation of protein complexes. Examples of adaptor proteins include MYD88, Grb2 and SHC1.
Much of the specificity of signal transduction depends on the recruitment of several signalling components such as protein kinases and G-protein GTPases into short-lived active complexes in response to an activating signal such as a growth factor binding to its receptor.
Adaptor proteins usually contain several domains within their structure (e.g., Src homology 2 (SH2) and SH3 domains) that allow specific interactions with several other specific proteins. SH2 domains recognise specific amino acid sequences within proteins containing phosphotyrosine residues and SH3 domains recognise proline-rich sequences within specific peptide sequence contexts of proteins.
There are many other types of interaction domains found within adaptor and other signalling proteins that allow a rich diversity of specific and coordinated protein–protein interactions to occur within the cell during signal transduction.
Genes encoding adaptor proteins include:
The SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.
The SH2domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins. SH2 domains are commonly found in adaptor proteins that aid in the signal transduction of receptor tyrosine kinase pathways.
Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.
Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene.
Lymphocyte cytosolic protein 2, also known as LCP2 or SLP-76, is a gene that encodes a signal-transducing adaptor protein.
The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.
GRB2-associated-binding protein 2 also known as GAB2 is a protein that in humans is encoded by the GAB2 gene.
Cbl is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.
Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene.
GRB2-associated-binding protein 1 is a protein that in humans is encoded by the GAB1 gene.
Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the FRS2 gene.
Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.
Receptor-type tyrosine-protein phosphatase alpha is an enzyme that in humans is encoded by the PTPRA gene.
TBK1 is an enzyme with kinase activity. Specifically, it is a serine / threonine protein kinase. It is encoded by the TBK1 gene in humans. This kinase is mainly known for its role in innate immunity antiviral response. However, TBK1 also regulates cell proliferation, apoptosis, autophagy, and anti-tumor immunity. Insufficient regulation of TBK1 activity leads to autoimmune, neurodegenerative diseases or tumorogenesis.
GRB2-related adapter protein 2 also known as GRB2-related adaptor downstream of Shc (GADS) is a 37 kDa protein that in humans is encoded by the GRAP2 gene.
Cytoplasmic protein NCK2 is a protein that in humans is encoded by the NCK2 gene.
Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene.
GRB2-related adapter protein is a protein that in humans is encoded by the GRAP gene.
A non-receptor tyrosine kinase (nRTK) is cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.