Tokiwa G, Dikic I, Lev S, Schlessinger J
Department of Pharmacology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.
Science. 1996 Aug 9;273(5276):792-4. doi: 10.1126/science.273.5276.792.
The c-Jun amino-terminal kinase (JNK) is activated by various heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, inflammatory cytokines, and stress signals. Yet, upstream mediators that link extracellular signals with the JNK signaling pathway are currently unknown. The tyrosine kinase Pyk2 was activated by tumor necrosis factor alpha, by ultraviolet irradiation, and by changes in osmolarity. Overexpression of Pyk2 led to activation of JNK, and a dominant-negative mutant of Pyk2 interfered with ultraviolet light- or osmotic shock-induced activation of JNK. Pyk2 represents a cell type-specific, stress-sensitive mediator of the JNK signaling pathway.
c-Jun氨基末端激酶（JNK）可被多种异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）偶联受体、炎性细胞因子及应激信号激活。然而，目前尚不清楚将细胞外信号与JNK信号通路相联系的上游介质。酪氨酸激酶Pyk2可被肿瘤坏死因子α、紫外线照射及渗透压变化激活。Pyk2的过表达导致JNK激活，而Pyk2的显性负性突变体则干扰紫外线或渗透压休克诱导的JNK激活。Pyk2代表了JNK信号通路中一种细胞类型特异性、应激敏感的介质。
