Vogel W, Lammers R, Huang J, Ullrich A
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Science. 1993 Mar 12;259(5101):1611-4. doi: 10.1126/science.7681217.
Regulation of cell proliferation, differentiation, and metabolic homeostasis is associated with the phosphorylation and dephosphorylation of specific tyrosine residues of key regulatory proteins. The phosphotyrosine phosphatase 1D (PTP 1D) contains two amino terminally located Src homology 2 (SH2) domains and is similar to the Drosophila corkscrew gene product, which positively regulates the torso tyrosine kinase signal transduction pathway. PTP activity was found to be regulated by physical interaction with a protein tyrosine kinase. PTP 1D did not dephosphorylate receptor tyrosine kinases, despite the fact that it associated with the epidermal growth factor receptor and chimeric receptors containing the extracellular domain of the epidermal growth factor receptor and the cytoplasmic domain of either the HER2-neu, kit-SCF, or platelet-derived growth factor beta (beta PDGF) receptors. PTP 1D was phosphorylated on tyrosine in cells overexpressing the beta PDGF receptor kinase and this tyrosine phosphorylation correlated with an enhancement of its catalytic activity. Thus, protein tyrosine kinases and phosphatases do not simply oppose each other's action; rather, they may work in concert to maintain a fine balance of effector activation needed for the regulation of cell growth and differentiation.
细胞增殖、分化和代谢稳态的调节与关键调节蛋白特定酪氨酸残基的磷酸化和去磷酸化有关。磷酸酪氨酸磷酸酶1D（PTP 1D）含有两个位于氨基末端的Src同源2（SH2）结构域，与果蝇螺旋基因产物相似，该产物正向调节躯干酪氨酸激酶信号转导途径。发现PTP活性受与蛋白酪氨酸激酶的物理相互作用调节。尽管PTP 1D与表皮生长因子受体以及含有表皮生长因子受体细胞外结构域和HER2-neu、kit-SCF或血小板衍生生长因子β（βPDGF）受体细胞质结构域的嵌合受体相关，但它不会使受体酪氨酸激酶去磷酸化。在过表达βPDGF受体激酶的细胞中，PTP 1D在酪氨酸上被磷酸化，这种酪氨酸磷酸化与其催化活性的增强相关。因此，蛋白酪氨酸激酶和磷酸酶并非简单地相互拮抗；相反，它们可能协同作用以维持调节细胞生长和分化所需的效应器激活的精细平衡。
