Pandey Akhilesh, Dan Ippeita, Kristiansen Troels Z, Watanabe Norinobu M, Voldby Jesper, Kajikawa Eriko, Khosravi-Far Roya, Blagoev Blagoy, Mann Matthias
Center for Experimental Bioinformatics, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Oncogene. 2002 May 30;21(24):3939-48. doi: 10.1038/sj.onc.1205478.
The p21-activated kinase (PAK) family of protein kinases has recently attracted considerable attention as an effector of Rho family of small G proteins and as an upstream regulator of MAPK signalling pathways during cellular events such as re-arrangement of the cytoskeleton and apoptosis. We have cloned a novel human PAK family kinase that has been designated as PAK5. PAK5 contains a CDC42/Rac1 interactive binding (CRIB) motif at the N-terminus and a Ste20-like kinase domain at the C-terminus. PAK5 is structurally most related to PAK4 and PAK6 to make up the PAK-II subfamily. We have shown that PAK5 preferentially binds to CDC42 in the presence of GTP and that CRIB motif is essential for this interaction. PAK5 is a functional protein kinase but unlike PAK-I family kinases (PAK1, 2, and 3), the kinase activity of PAK5 does not seem to require the binding of CDC42. Overexpression of PAK5 activates the JNK kinase pathway but not p38 or ERK pathways. PAK5 transcript is predominantly expressed in brain as revealed by Northern blot and in situ hybridization. The expression pattern of PAK5 is distinct from that of PAK4 and PAK6, suggesting a functional division among PAK-II subfamily kinases based on differential tissue distribution.
p21激活激酶（PAK）蛋白激酶家族最近作为小G蛋白Rho家族的效应器以及细胞事件（如细胞骨架重排和凋亡）期间MAPK信号通路的上游调节因子，引起了相当大的关注。我们克隆了一种新的人类PAK家族激酶，命名为PAK5。PAK5在N端含有一个CDC42/Rac1相互作用结合（CRIB）基序，在C端含有一个Ste20样激酶结构域。PAK5在结构上与PAK4和PAK6关系最为密切，构成PAK-II亚家族。我们已经表明，PAK5在GTP存在的情况下优先与CDC42结合，并且CRIB基序对于这种相互作用至关重要。PAK5是一种功能性蛋白激酶，但与PAK-I家族激酶（PAK1、2和3）不同，PAK5的激酶活性似乎不需要CDC42的结合。PAK5的过表达激活JNK激酶途径，但不激活p38或ERK途径。Northern印迹和原位杂交显示，PAK5转录本主要在脑中表达。PAK5的表达模式与PAK4和PAK6不同，这表明基于不同的组织分布，PAK-II亚家族激酶之间存在功能划分。
