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Amino-acid sequence motifs for PKC-mediated membrane trafficking of the inhibitory killer Ig-like receptor

Authors
 Yong-Joon Chwae  ;  Jae Myun Lee  ;  Hyung-Ran Kim  ;  Eun Joo Kim  ;  Seung Tae Lee  ;  Jae-Won Soh  ;  Jongsun Kim 
Citation
 Immunology and Cell Biology, Vol.86(4) : 372-380, 2008 
Journal Title
 Immunology and Cell Biology 
ISSN
 0818-9641 
Issue Date
2008
Abstract
Activation-induced upregulation of inhibitory killer Ig-like receptor (KIR) is regulated by protein kinase Cs (PKCs). Conventional PKCs increase KIR expression on the post-transcriptional level by increasing the recycling of surface molecules and endoplasmic reticulum (ER)-Golgi processing. PKCdelta plays a role in the secretion of cytoplasmic KIR through lytic granules. In this study, we identified amino acid sequence motifs associated with PKC-mediated KIR membrane trafficking by systematic mutagenesis. Mutations of Y(398) and HLWC(364) completely inhibited the PMA-induced increase of KIR molecules at surface as well as total protein levels, indicating that these are associated with ER-Golgi processing and sorting to plasma membrane through lytic granules. Mutations of Y-based motif, including Y(398), acidic region (PE(394)), dileucine motif-like region (IL(423)) and PKC-phosphorylatable S(415) caused a blockade of surface KIR endocytosis after PKC stimulation. Mutation of T(145) caused an accumulation of mutant proteins in late endosomes and lysosomes after PKC activation, suggesting that T(145) might be related to the recovery of endocytosed KIR to the surface membrane. We also demonstrated that PKCs could directly phosphorylate the KIR cytoplasmic tail by means of western blot and in vitro kinase assay, implying that phosphorylation status of KIR cytoplasmic tail can direct the fate of surface KIR molecules. Taken together, various sequence motifs are implicated in the PKC-mediated post-transcriptional upregulation of KIR, and each of these motifs work in different steps after PKC activation.
Full Text
http://www.nature.com/icb/journal/v86/n4/full/icb20085a.html
DOI
10.1038/icb.2008.5
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김종선(Kim, Jong Sun) ORCID logo https://orcid.org/0000-0002-3149-669X
김형란(Kim, Hyung Ran)
이승태(Lee, Seung Tae)
이재면(Lee, Jae Myun) ORCID logo https://orcid.org/0000-0002-5273-3113
최용준(Chwae, Yong Joon)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106677
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