Chow L M, Jarvis C, Hu Q, Nye S H, Gervais F G, Veillette A, Matis L A
McGill Cancer Centre, McGill University, Montreal, PQ, Canada.
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4975-9. doi: 10.1073/pnas.91.11.4975.
The activity of Src-related protein-tyrosine kinases is repressed by the phosphorylation of a conserved carboxyl-terminal tyrosine by another cytoplasmic protein-tyrosine kinase termed p50csk. In this study, we characterize Ntk, a protein-tyrosine kinase bearing striking similarities to p50csk. Like p50csk, Ntk possesses Src homology 3 and Src homology 2 domains and lacks the consensus tyrosine phosphorylation and myristoylation sites found in members of the Src family. Expression of ntk transcripts was maximal in brain, and was observed at significant levels in thymus and spleen. ntk RNA levels were dramatically reduced upon mitogenic stimulation of normal T lymphocytes and were minimal in transformed T-cell populations. Firm evidence that Ntk is a Csk-related enzyme was provided by the observation that it phosphorylated a Src-related polypeptide on the inhibitory carboxyl-terminal tyrosine. These findings indicate that Ntk is a Csk-related enzyme that may play an inhibitory role in the control of T-cell proliferation.
一种名为p50csk的胞质蛋白酪氨酸激酶通过对保守的羧基末端酪氨酸进行磷酸化，来抑制与Src相关的蛋白酪氨酸激酶的活性。在本研究中，我们鉴定了Ntk，一种与p50csk具有显著相似性的蛋白酪氨酸激酶。与p50csk一样，Ntk拥有Src同源结构域3和Src同源结构域2，并且缺乏Src家族成员中常见的酪氨酸磷酸化共有序列和豆蔻酰化位点。ntk转录本在脑中的表达量最高，在胸腺和脾脏中也有显著水平的表达。正常T淋巴细胞经有丝分裂原刺激后，ntk RNA水平显著降低，而在转化的T细胞群体中则降至最低。通过观察到Ntk能使一种与Src相关的多肽的抑制性羧基末端酪氨酸发生磷酸化，有力地证明了Ntk是一种与Csk相关的酶。这些发现表明，Ntk是一种与Csk相关的酶，可能在T细胞增殖控制中发挥抑制作用。
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