Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins
Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins
复制标题
DOI：
10.1074/jbc.m303221200
复制
发表时间：
2003-09-05
影响因子：
4.8
通讯作者：
Johansen, T
中科院分区：
文献类型：
--
作者：
Lamark, T;Perander, M;Johansen, T
Phox和Bem1p（PB1）结构域是最近发现的一种蛋白质 - 蛋白质相互作用结构域，存在于非典型蛋白激酶C（aPKC）同工酶λ/iota和zetaPKC中；也存在于有丝分裂原活化蛋白激酶（MAPK）模块成员如MEK5、MEKK2和MEKK3中；还存在于一些参与细胞信号传导的支架蛋白中。在最后一组中，p62和Par6（分区缺陷蛋白6）参与将aPKC与涉及细胞存活、生长控制和细胞极性的信号通路偶联。通过突变分析和分子建模，我们已经确定了aPKC和p62的PB1结构域相互作用表面的关键残基。在p62寡聚化以及aPKC - p62相互作用中，一个碱性电荷簇与一个酸性环和螺旋相互作用。随后，我们确定了哺乳动物PB1结构域蛋白通过该结构域形成异聚体和同聚体复合物的能力。我们报道了这个家族内的几种新的相互作用。发现了细胞极性支架蛋白Par6和MEK5之间的相互作用。此外，除了与aPKC相互作用外，p62还与MEK5和NBR1相互作用。文中还提供了p62参与MEK5 - ERK5信号传导的证据。
The Phox and Bem1p (PB1) domain constitutes a recently recognized protein-protein interaction domain found in the atypical protein kinase C ( aPKC) isoenzymes, lambda/iota and zetaPKC; members of mitogen-activated protein kinase (MAPK) modules like MEK5, MEKK2, and MEKK3; and in several scaffold proteins involved in cellular signaling. Among the last group, p62 and Par6 (partitioning-defective 6) are involved in coupling the aPKCs to signaling pathways involved in cell survival, growth control, and cell polarity. By mutation analyses and molecular modeling, we have identified critical residues at the interaction surfaces of the PB1 domains of aPKCs and p62. A basic charge cluster interacts with an acidic loop and helix both in p62 oligomerization and in the aPKC-p62 interaction. Subsequently, we determined the abilities of mammalian PB1 domain proteins to form heteromeric and homomeric complexes mediated by this domain. We report several novel interactions within this family. An interaction between the cell polarity scaffold protein Par6 and MEK5 was found. Furthermore, p62 interacts both with MEK5 and NBR1 in addition to the aPKCs. Evidence for involvement of p62 in MEK5-ERK5 signaling is presented.