Regulation of Protein Serine-Threonine Phosphatase Type-2A by Tyrosine Phosphorylation

• Published in: Science (American Association for the Advancement of Science) Vol. 257; no. 5074; pp. 1261 - 1264
• Main Authors: Chen, Jian, Martin, Bruce L., Brautigan, David L.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 28.08.1992
• Subjects: Analytical, structural and metabolic biochemistry; Animal cells; Animals; Antibodies; Biological and medical sciences; catalytic subunits; Cellular signal transduction; Enzymes and enzyme inhibitors; ErbB Receptors - physiology; Ethers, Cyclic - pharmacology; Fundamental and applied biological sciences. Psychology; Gels; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Hormones; Humans; Hydrolases; In Vitro Techniques; Insulin; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); man; Okadaic Acid; Oncogene Protein pp60(v-src) - pharmacology; Phosphatases; Phosphoamino acids; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Phosphorylation - drug effects; Photographic film; Protein kinases; Protein Phosphatase 2; protein serine-threonine phosphatase 2A; Protein-Tyrosine Kinases - physiology; Rabbits; Receptor, Insulin - physiology; Receptors; regulation; Thionucleotides - pharmacology; tyrosine; Tyrosine - metabolism; Signal transduction; Dephosphorylation; Enzymatic activity; Enzyme; Phosphoprotein phosphatase; Regularity
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1325671

Extracellular signals that promote cell growth activate cascades of protein kinases. The kinases are dephosphorylated and deactivated by a single type-2A protein phosphatase. The catalytic subunit of type-2A protein phosphatase was phosphorylated by tyrosine-specific protein kinases. Phosphorylation was enhanced in the presence of the phosphatase inhibitor okadaic acid, consistent with an autodephosphorylation reaction. More than 90% of the activity of phosphatase 2A was lost when thioadenosine triphosphate was used to produce a thiophosphorylated protein resistant to autodephosphorylation. Phosphorylation in vitro occurred exclusively on Tyr$^{307}$. Phosphorylation was catalyzed by p60$^{v-src}$, p56$^{lck}$, epidermal growth factor receptors, and insulin receptors. Transient deactivation of phosphatase 2A might enhance transmission of cellular signals through kinase cascades within cells.