Signal transducing adaptor protein

Src-associated adaptor protein Skap2 with 1u5e code

Signal transducing adaptor proteins (STAPs) are proteins that are accessory to main proteins in a signal transduction pathway. ^[1] 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, ^[2] instead mediating specific protein–protein interactions that drive the formation of protein complexes. Examples of adaptor proteins include MYD88, ^{[3] [4]} Grb2 and SHC1.

Signaling components

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.

Domains

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.

Examples of adaptor proteins

Adaptor proteins include:

• BCAR3 – Breast cancer anti-estrogen resistance protein 3
• CBL – Casitas B-lineage Lymphoma
• FRS2 – Fibroblast growth factor receptor substrate 2
• GAB2 – GRB2-associated binding protein 2
• GRAP – GRB2-related adaptor protein
• GRAP2 – GRB2-related adaptor protein 2
• GRB2 – Growth factor receptor-bound protein 2
• IRS1 – Insulin receptor substrate 1
• LDLRAP1 – low-density lipoprotein receptor adaptor protein 1
• MYD88 - Myeloid differentiation primary response gene 88
• NCDN - Neurochondrin
• NCK1 – NCK adaptor protein 1
• NCK2 – NCK adaptor protein 2
• NOS1AP – nitric oxide synthase 1 (neuronal) adaptor protein
• PIK3AP1 – phosphoinositide-3-kinase adaptor protein 1
• SH2B1 – SH2B adaptor protein 1
• SH2B2 – SH2B adaptor protein 2
• SH2B3 – SH2B adaptor protein 3
• SH2D3A -SH2 domain containing 3A
• SH2D3C – SH2 domain containing 3C
• SNTA1 – Syntrophin, alpha 1
• SHB – Src homology 2 domain containing adaptor protein B
• SLC4A1AP – solute carrier family 4 (anion exchanger), member 1, adaptor protein

See also

• Wikipedia:MeSH D12.776#MeSH D12.776.157.057 --- adaptor proteins.2C signal transducing
• Wikipedia:MeSH D12.776#MeSH D12.776.543.990.150 --- adaptor proteins.2C vesicular transport

References

1. Toda, Jun; Ichii, Michiko; Shibayama, Hirohiko; Saito, Hideaki; Kitai, Yuichi; Muromoto, Ryuta; Kashiwakura, Jun-Ichi; Saitoh, Kodai; Matsuda, Tadashi; Oritani, Kenji; Kanakura, Yuzuru (7 December 2017). "Role of Signal Transducing Adaptor Protein (STAP) Family in Chronic Myelogenous Leukemia". Blood. 130 (Supplement 1): 1583. Retrieved 24 August 2018.
2. Signal+Transducing+Adaptor+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
3. "Entrez Gene: MYD88 Myeloid differentiation primary response gene (88)".
4. Bonnert TP, Garka KE, Parnet P, Sonoda G, Testa JR, Sims JE (January 1997). "The cloning and characterization of human MyD88: a member of an IL-1 receptor related family". FEBS Letters. 402 (1): 81–4. doi: 10.1016/S0014-5793(96)01506-2 . PMID   9013863. S2CID   44843127.

Further reading

• TAB2 is an adaptor protein involved in the IL-1 signal transduction pathway: Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K (April 2000). "TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway". Molecular Cell. 5 (4): 649–58. doi: 10.1016/S1097-2765(00)80244-0 . PMID   10882101.
• Good article about adaptor proteins involved in protein kinase C-mediated signal transduction: Schechtman D, Mochly-Rosen D (October 2001). "Adaptor proteins in protein kinase C-mediated signal transduction". Oncogene. 20 (44): 6339–47. doi: 10.1038/sj.onc.1204778 . PMID   11607837.
• A good article regarding the role of adaptor proteins involved with the T-cell antigen receptor: Samelson LE (2002). "Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins". Annual Review of Immunology. 20 (1): 371–94. doi:10.1146/annurev.immunol.20.092601.111357. PMID   11861607.
• Signalling discussed with regard to adaptor proteins: Pawson, T. (1997). "Signaling Through Scaffold, Anchoring, and Adaptor Proteins". Science. 278 (5346): 2075–2080. Bibcode:1997Sci...278.2075P. doi:10.1126/science.278.5346.2075. ISSN   0036-8075. PMID   9405336.