The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis
The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis
复制标题
DOI：
10.1074/jbc.m011046200
复制
发表时间：
2001-04-27
影响因子：
4.8
通讯作者：
Minden, A
中科院分区：
文献类型：
--
作者：
Gnesutta, N;Qu, J;Minden, A
丝氨酸/苏氨酸激酶 PAK4 首先被鉴定为 Rho GTPase Cdc42 的效应分子。 PAK4 在序列和功能上都不同于 PAK 家族的其他成员。之前我们已经证明该激酶的一个重要功能是响应激活的 Cdc42 介导丝状伪足的诱导。对组成型活性 PAK4 突变体的研究表明，它还具有促进锚定非依赖性生长的作用，这是致癌转化的重要标志。在这里，我们证明 PAK4 的另一个功能是保护细胞免遭细胞凋亡。野生型或组成型活性 PAK4 的表达可延迟肿瘤坏死因子 LY 刺激、紫外线照射和血清饥饿引起的细胞凋亡的发生。与抗凋亡功能一致，PAK4 的表达导致促凋亡蛋白 Bad 磷酸化增加并抑制 caspase 激活。
The serine/threonine kinase PAK4 was identified first as an effector molecule for the Rho GTPase Cdc42. PAK4 differs from other members of the PAK family both in sequence and function. Previously we have shown that an important function of this kinase is to mediate the induction of filopodia in response to activated Cdc42. Studies with a, constitutively active PAK4 mutant have shown that it also has a role in promoting anchorage-independent growth, an important hallmark of oncogenic transformation. Here we show that another function of PAK4 is to protect cells against apoptotic cell death. Expression of wild-type or constitutively active PAK4 delays the onset of apoptosis in response to tumor necrosis factor LY stimulation, UV irradiation, and serum starvation. Consistent with an antiapoptotic function, expression of PAK4 leads to an increase in phosphorylation of the proapoptotic protein Bad and an inhibition of caspase activation.