Description
Phosphatidylinositol 3-kinase (PI3K) p85 alpha is a regulatory subunit that heterodimerizes with a catalytic subunit to form a Class IA PI3K enzyme complex, which plays an important role in the immune system (1,2). The P13K pathway is involved in many diverse processes including growth, metabolism, proliferation, and survival (2). PI3Ks are typically activated by cytokine receptors and are responsible for phosphorylation of the 3'-hydroxyl group of PI and its derivatives (3). p85 alpha is one of five regulatory subunit proteins which also includes p55 alpha, p50 alpha, p85 beta, and p55 gamma, and can bind to two of the three catalytic subunits (p110 alpha or p110 delta) (1,2). p85 alpha, p55 alpha, and p50 alpha proteins are all synthesized by the same PIK3R1 gene by alternative splicing (1). Structurally, PI 3-Kinase p85 alpha contains SRC homology 3 (SH3 domain), followed by a Bcr homology (BH) domain flanked by two proline-rich regions, then a N-terminal SH2 domain, an inter-SH2 domain, and C-terminal SH2 domain (1,2). PI 3-Kinase p85 alpha protein consists of 724 amino acids (aa) in length with a theoretical molecular weight of 83.5 kDa (2,4). The primary role for the p85 subunit is interaction with cell surface receptors and acts as an adapter for the stabilization and recruitment of the p110 catalytic subunit to the plasma membrane (1,3). Additionally, p85 has been shown to function in both interleukin-2 receptor (IL2R) and erythropoietin receptor (EpoR) endocytosis (3).
The PI3K pathway functions in a broad range of cellular processes, so it is understandable that pathway dysfunction can lead to an array of diseases and disorders (2,5). Elevated PI3K signaling is a key feature of many cancers (5). PI3K pathway dysregulation has also been implicated in neurological, metabolic, and cardiovascular disorders (5). Furthermore, both overactivation or under-activation of the PI3K delta (p85 alpha subunit + p110 delta subunit) pathway has been shown to cause immunodeficiency and pathologies related to immune system dysfunction (2). Therapeutics to target the PI3K pathway and treat related cancers include PI3K inhibitors and, specifically, isoform-selective inhibitors which have a lot of promise when used as part of a combination therapy (5).
References
1. Okkenhaug, K., & Vanhaesebroeck, B. (2001). New responsibilities for the PI3K regulatory subunit p85 alpha. Science's STKE : signal transduction knowledge environment. https://doi.org/10.1126/stke.2001.65.pe1
2. Nunes-Santos, C. J., Uzel, G., & Rosenzweig, S. D. (2019). PI3K pathway defects leading to immunodeficiency and immune dysregulation. The Journal of allergy and clinical immunology. https://doi.org/10.1016/j.jaci.2019.03.017
3. Chen, P. H., Yao, H., & Huang, L. J. (2017). Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent Roles of PI3K. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2017.00078
4. Uniprot (P27986)
5. Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017). The PI3K Pathway in Human Disease. Cell. https://doi.org/10.1016/j.cell.2017.07.029
Bioinformatics
| Entrez |
Mouse
Mouse
Rat
Rat
Rat
Human
|
| Uniprot |
Human
Human
Human
Human
Human
|
| Product By Gene ID |
5295 |
| Alternate Names |
- AGM7
- GRB1
- IMD36
- p85
- p85-ALPHA
- Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
- phosphatidylinositol 3-kinase regulatory subunit alpha
- phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha)
- phosphatidylinositol 3-kinase-associated p-85 alpha
- phosphoinositide-3-kinase regulatory subunit alpha
- phosphoinositide-3-kinase, regulatory subunit 1 (alpha)
- PI3K regulatory subunit alpha
- PI3-kinase regulatory subunit alpha
- PI3-kinase subunit p85-alpha
- PIK3R1
- PtdIns-3-kinase regulatory subunit alpha
- PtdIns-3-kinase regulatory subunit p85-alpha
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