RAS-DEPENDENT GROWTH-FACTOR REGULATION OF MEK KINASE IN PC12 CELLS
RAS-DEPENDENT GROWTH-FACTOR REGULATION OF MEK KINASE IN PC12 CELLS
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DOI：
10.1126/science.8073291
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发表时间：
1994-09-02
期刊：
影响因子：
56.9
通讯作者：
JOHNSON, GL
中科院分区：
文献类型：
--
作者：
LANGECARTER, CA;JOHNSON, GL
丝裂原激活蛋白激酶（MAPK）响应不同受体类型的刺激而迅速激活。 MAPK 通过 MAP 激酶或细胞外信号调节激酶 (ERK) 激酶 (MEK) 对苏氨酸和酪氨酸的磷酸化进行正向调节。 MEK 激酶 (MEKK) 是丝氨酸-苏氨酸蛋白激酶家族的一部分，可独立于 Raf 磷酸化和激活 MEK。 MEKK 在表皮生长因子 (EGF) 刺激静息 PC12 细胞时被快速且持续地激活。神经生长因子 (NGF) 和 12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 也能激活 MEKK，但程度低于 EGF。 MEKK 和 B-Raf 响应 EGF 的激活受到显性失活 N(17)Ras 表达的抑制。致癌 Ras 的表达导致 MEKK 的激活。环腺苷 3',5'-单磷酸合成的刺激消除了 EGF、NGF 和 TPA 对 MEKK 和 B-Raf 的激活。因此，Ras 同时控制蛋白激酶 Raf 和 MEKK 家族成员的激活。
Mitogen-activated protein kinases (MAPKs) are rapidly activated in response to stimulation of diverse receptor types. MAPKs are positively regulated by phosphorylation on threonine and tyrosine by MAP kinase or extracellular signal-regulated kinase (ERK) kinases (MEKs). MEK kinase (MEKK) is part of a family of serine-threonine protein kinases that phosphorylate and activate MEKs independently of Raf. MEKK was rapidly and persistently activated in response to stimulation of resting PC12 cells with epidermal growth factor (EGF). Nerve growth factor (NGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) also activated MEKK, although to a lesser degree than did EGF. Activation of MEKK and B-Raf in response to EGF was inhibited by expression of dominant negative N(17)Ras. Expression of oncogenic Ras resulted in activation of MEKK. Stimulation of synthesis of cyclic adenosine 3',5'-monophosphate abolished activation of MEKK and B-Raf by EGF, NGF, and TPA. Thus, Ras simultaneously controls the activation of members of the Raf and MEKK families of protein kinases.