Functional analysis of a Novel Human Protein Kinase, Nori-2p (MRPK) in the Proliferation of Cancer Cells

在淋巴因子活化的t -杀伤细胞（T-LAK）细胞减法文库中发现了一种新的人丝氨酸/苏氨酸激酶，并克隆了人和小鼠的全长cDNA。这种蛋白激酶，即膜淋巴毒素相关蛋白激酶（MRPK/Nori-2p），具有丝氨酸/苏氨酸激酶基序，似乎是酵母丝氨酸/苏氨酸激酶YGR262c的同源物。与YGR 262c相似，MRPK不具备一些典型的蛋白激酶序列模式，但在体外可进行酪蛋白磷酸化。MRPK mRNA在睾丸组织中有明显表达。活化而非失活的T-LAK细胞表达MRPK mRNA。在一些肿瘤细胞系中发现了天然MRPK转录物，mRNA也有表达。MRPK具有酵母YGR262c中不存在的双核定位信号（NLS_BP）。免疫组化研究显示MRPK定位于细胞核。利用YGR262c中断酵母进行的互补实验表明，MRPK可能不是YGR262c的功能同源物。同步细胞周期研究表明，MRPK mRNA仅出现在s期。这些结果表明，一种新的蛋白激酶MRPK可能在IL-2驱动的T-LAK细胞和一些癌细胞的增殖中发挥重要作用。

A novel human serine/threonine kinase was identified in a Lymphokine-activated T-killer (T-LAK) cell subtraction library and full length cDNA of both human and mouse were cloned. This protein kinase, namely membrane lymphotoxin-related protein kinase (MRPK/Nori-2p), possesses a serine/threonine kinase motif and appears to be a homologue of a yeast serine/threonine kinase, YGR262c. Similar with YGR 262c, MRPK fails to have some typical sequence patterns of protein kinase but it exerts casein phosphorylation in vitro. The expression of MRPK mRNA was noted markedly in the testicular tissue. The activated but not deactivated form of T-LAK cells express MRPK mRNA.Natural MRPK transcript was identified in some cancer cell lines along with the mRNA expression. MRPK indicated to have a bipartite nuclear localization signal (NLS_BP) that does not exist in the yeast YGR262c. Immunohistochemical study showed that MRPK localizes in the nucleus. A complementation assay using YGR262c-disrupted yeast showed that MRPK may not be a functional homologue of YGR262c. A synchronized cell cycle study showed that MRPK mRNA appeared only in the S-phase. These results suggest that a novel protein kinase, MRPK, may play some important roles in the proliferation of IL-2 driven T-LAK cells and some cancer cells.