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

从人T淋巴细胞杀伤（T-LAK）细胞消减文库中鉴定出一种新的人丝氨酸/苏氨酸激酶，并克隆了人和小鼠的全长cDNA。这种蛋白激酶，即膜光蛋白相关蛋白激酶（MRPK/Nori-2 p），具有丝氨酸/苏氨酸激酶基序，并且似乎是酵母丝氨酸/苏氨酸激酶YGR 262 c的同源物。与YGR 262 c相似，MRPK不具有蛋白激酶的一些典型序列模式，但在体外发挥酪蛋白磷酸化作用。MRPK mRNA在睾丸组织中有明显表达。活化的T-LAK细胞表达MRPK mRNA，在某些肿瘤细胞株中，随着mRNA的表达，还发现了天然的MRPK转录本沿着。MRPK表明具有在酵母YGR 262 c中不存在的二分核定位信号（NLS_BP）。免疫组化显示MRPK定位于细胞核。使用YGR 262 c破坏的酵母的互补测定表明，MRPK可能不是YGR 262 c的功能同源物。细胞周期同步化研究表明，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细胞和某些癌细胞的增殖中起重要作用。

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.