Kuwana T, Peterson P A, Karlsson L
The R. W. Johnson Pharmaceutical Research Institute, 3535 General Atomics Court, Suite 100, San Diego, CA 92121, USA.
Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1056-61. doi: 10.1073/pnas.95.3.1056.
The Iip35 isoform of the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) contains an endoplasmic reticulum (ER) targeting motif, but in B cell lines the ER retention is ineffective and a fraction of Iip35 is transported through the Golgi complex associated with class II molecules. We found Iip35 (but not Iip33, the major form of Ii) to be phosphorylated in B cell lines, as well as in transfected HeLa cells. The phosphorylation of Iip35 was found to be necessary for the exit of Iip35-class II complexes out of the ER. This requirement suggests that phosphorylation may change the interaction with factors responsible for ER retention/retrieval, and we did find that phosphorylated Iip35 associates with 14-3-3 proteins, a family of adaptor proteins that are involved in coordinating signal transduction pathways. This finding raises the intriguing possibility that the exit of Ii-class II complexes from the ER is regulated by intracellular signaling events.
主要组织相容性复合体（MHC）II类相关恒定链（Ii）的Iip35异构体含有一个内质网（ER）靶向基序，但在B细胞系中，内质网保留无效，一部分Iip35与II类分子一起通过高尔基体复合体转运。我们发现Iip35（而非Ii的主要形式Iip33）在B细胞系以及转染的HeLa细胞中被磷酸化。Iip35的磷酸化被发现是Iip35-II类复合物从内质网输出所必需的。这一需求表明磷酸化可能改变与负责内质网保留/回收的因子的相互作用，并且我们确实发现磷酸化的Iip35与14-3-3蛋白相关联，14-3-3蛋白是一类参与协调信号转导途径的衔接蛋白家族。这一发现引发了一个有趣的可能性，即Ii-II类复合物从内质网的输出受细胞内信号事件调控。
