Mourey R J, Vega Q C, Campbell J S, Wenderoth M P, Hauschka S D, Krebs E G, Dixon J E
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109-0606, USA.
J Biol Chem. 1996 Feb 16;271(7):3795-802. doi: 10.1074/jbc.271.7.3795.
Dual specificity protein tyrosine phosphatases (dsPTPs) are a subfamily of protein tyrosine phosphatases implicated in the regulation of mitogen-activated protein kinase (MAPK). In addition to hydrolyzing phosphotyrosine, dsPTPs can hydrolyze phosphoserine/threonine-containing substrates and have been shown to dephosphorylate activated MAPK. We have identified a novel dsPTP, rVH6, from rat hippocampus. rVH6 contains the conserved dsPTP active site sequence, VXVHCX2GX2RSX5AY(L/I)M, and exhibits phosphatase activity against activated MAPK. In PC12 cells, rVH6 mRNA is induced during nerve growth factor-mediated differentiation but not during insulin or epidermal growth factor mitogenic stimulation. In MM14 muscle cells, rVH6 mRNA is highly expressed in proliferating cells and declines rapidly during differentiation. rVH6 expression correlates with the inability of fibroblast growth factor to stimulate MAPK activity in proliferating but not in differentiating MM14 cells. rVH6 protein localizes to the cytoplasm and is the first dsPTP to be localized outside the nucleus. This novel subcellular localization may expose rVH6 to potential substrates that differ from nuclear dsPTPs substrates.
双特异性蛋白酪氨酸磷酸酶（dsPTPs）是蛋白酪氨酸磷酸酶的一个亚家族，参与有丝分裂原激活蛋白激酶（MAPK）的调节。除了水解磷酸酪氨酸外，dsPTPs还能水解含磷酸丝氨酸/苏氨酸的底物，并已被证明能使活化的MAPK去磷酸化。我们从大鼠海马体中鉴定出一种新型的dsPTP，rVH6。rVH6包含保守的dsPTP活性位点序列VXVHCX2GX2RSX5AY(L/I)M，并对活化的MAPK表现出磷酸酶活性。在PC12细胞中，rVH6 mRNA在神经生长因子介导的分化过程中被诱导，但在胰岛素或表皮生长因子促有丝分裂刺激过程中不被诱导。在MM14肌肉细胞中，rVH6 mRNA在增殖细胞中高度表达，在分化过程中迅速下降。rVH6的表达与成纤维细胞生长因子在增殖的MM14细胞中而非分化的MM14细胞中刺激MAPK活性的能力相关。rVH6蛋白定位于细胞质，是首个定位于细胞核外的dsPTP。这种新的亚细胞定位可能使rVH6接触到与核dsPTP底物不同的潜在底物。
