hVH-5: a protein tyrosine phosphatase abundant in brain that inactivates mitogen-activated protein kinase.
A novel protein tyrosine phosphatase [homologue of vaccinia virus H1 phosphatase gene clone 5 (hVH-5)] was cloned; it shared sequence similarity with a subset of protein tyrosine phosphatases that regulate mitogen-activated protein kinase. The catalytic region of hVH-5 was expressed as a fusion protein and was shown to hydrolyze p-nitrophenylphosphate and inactivate mitogen-activated protein kinase, thus proving that hVH-5 possessed phosphatase activity. A unique proline-rich region distinguished hVH-5 from other closely related protein tyrosine phosphatases. Another feature that distinguished hVH-5 from related phosphatases was that hVH-5 was expressed predominantly in the adult brain, heart, and skeletal muscle. In addition, in situ hybridization histochemistry of mouse embryo revealed high levels of expression and a wide distribution in the central and peripheral nervous system. Some specific areas of abundant hVH-5 expression included the olfactory bulb, retina, layers of the cerebral cortex, and cranial and spinal ganglia. hVH-5 was induced in PC12 cells upon nerve growth factor and insulin treatment in a manner characteristic of an immediate-early gene, suggesting a possible role in the signal transduction cascade.
Martell
K J
KJ
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109, USA.
Seasholtz
A F
AF
Kwak
S P
SP
Clemens
K K
KK
Dixon
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D002454:Cell Differentiation; D003001:Cloning, Molecular; D054637:Dual-Specificity Phosphatases; D004789:Enzyme Activation; D017403:In Situ Hybridization; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016716:PC12 Cells / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D014018:Tissue Distribution
D008934:Mitogens; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; C517038:DUSP8 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases