Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation.
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.
Chen
J
J
Division of Biology and Medicine, Brown University, Providence, RI 02912.
Martin
B L
BL
Brautigan
D L
DL
D000818:Animals; D066246:ErbB Receptors / Q000502:physiology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019319:Okadaic Acid; D015688:Oncogene Protein pp60(v-src) / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011817:Rabbits; D011972:Receptor, Insulin / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*
D004988:Ethers, Cyclic; D013873:Thionucleotides; D019319:Okadaic Acid; C001707:6-thioinosine-5'-triphosphate; D014443:Tyrosine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D015688:Oncogene Protein pp60(v-src); D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2