okadaic-acid and 6-thioinosine-5--triphosphate

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 Tyr307. Phosphorylation was catalyzed by p60v-src, p56lck, epidermal growth factor receptors, and insulin receptors. Transient deactivation of phosphatase 2A might enhance transmission of cellular signals through kinase cascades within cells.

Topics: Animals; ErbB Receptors; Ethers, Cyclic; Gene Expression Regulation; Humans; In Vitro Techniques; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Okadaic Acid; Oncogene Protein pp60(v-src); Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 2; Protein-Tyrosine Kinases; Rabbits; Receptor, Insulin; Thionucleotides; Tyrosine