Hurov J B, Stappenbeck T S, Zmasek C M, White L S, Ranganath S H, Russell J H, Chan A C, Murphy K M, Piwnica-Worms H
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
Mol Cell Biol. 2001 May;21(9):3206-19. doi: 10.1128/MCB.21.9.3206-3219.2001.
Emk is a serine/threonine protein kinase implicated in regulating polarity, cell cycle progression, and microtubule dynamics. To delineate the role of Emk in development and adult tissues, mice lacking Emk were generated by targeted gene disruption. Emk(-/-) mice displayed growth retardation and immune cell dysfunction. Although B- and T-cell development were normal, CD4(+)T cells lacking Emk exhibited a marked upregulation of the memory marker CD44/pgp-1 and produced more gamma interferon and interleukin-4 on stimulation through the T-cell receptor in vitro. In addition, B-cell responses to T-cell-dependent and -independent antigen challenge were altered in vivo. As Emk(-/-) animals aged, they developed splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Taken together, these results demonstrate that the Emk protein kinase is essential for maintaining immune system homeostasis and that loss of Emk may contribute to autoimmune disease in mammals.
Emk是一种丝氨酸/苏氨酸蛋白激酶，与调节细胞极性、细胞周期进程和微管动力学有关。为了阐明Emk在发育和成年组织中的作用，通过靶向基因敲除产生了缺乏Emk的小鼠。Emk(-/-)小鼠表现出生长迟缓以及免疫细胞功能障碍。虽然B细胞和T细胞发育正常，但缺乏Emk的CD4(+)T细胞表现出记忆标记CD44/pgp-1的显著上调，并且在体外通过T细胞受体刺激时产生更多的γ干扰素和白细胞介素-4。此外，B细胞对T细胞依赖性和非依赖性抗原刺激的反应在体内发生了改变。随着Emk(-/-)动物年龄增长，它们出现脾肿大、淋巴结病、膜增生性肾小球肾炎以及肺部、腮腺和肾脏中的淋巴细胞浸润。综上所述，这些结果表明Emk蛋白激酶对于维持免疫系统稳态至关重要，并且Emk的缺失可能导致哺乳动物自身免疫性疾病。
