Protein phosphatase 2A forms a molecular complex with Shc and regulates Shc tyrosine phosphorylation and downstream mitogenic signaling
Abstract
Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase that carries out multiple functions. Although numerous observations suggest that PP2A plays a major role in downregulation of the mitogen-activated protein (MAP) kinase pathway, the precise mechanisms are unknown. To clarify the role of PP2A in growth factor (insulin, epidermal growth factor [EGF], and insulin-like growth factor 1 [IGF-1]) stimulation of the Ras/MAP kinase pathway, simian virus 40 small t antigen was expressed in Rat-1 fibroblasts which overexpress insulin receptors. Small t antigen is known to specifically inhibit PP2A by binding to the A PP2A regulatory subunit, interfering with the ability of PP2A to bind to its cellular substrates. Overexpressed small t protein was coimmunoprecipitated with PP2A and inhibited cellular PP2A activity but did not inhibit protein phosphatase 1 (PP1) activity. Insulin, IGF-1, and EGF stimulation also inhibited PP2A activity. Growth factor-stimulated Ras, Raf-1, MAP kinase, and mitogen-activated extracellular-signal-regulated kinase kinase (MEK) activities were elevated in small-t-antigen-expressing cells. Furthermore, Shc tyrosine phosphorylation and its association with Grb2 were also elevated in small-t...Continue Reading
References
Citations
Protein phosphatase 2A regulatory subunit Bbeta promotes MAP kinase-mediated migration of A431 cells
Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase
Related Concepts
Trending Feeds
COVID-19
Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.
Synthetic Genetic Array Analysis
Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.
Congenital Hyperinsulinism
Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.
Neural Activity: Imaging
Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.
Chronic Fatigue Syndrome
Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.
Epigenetic Memory
Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.
Cell Atlas of the Human Eye
Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.
Femoral Neoplasms
Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.
STING Receptor Agonists
Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.