title: The cytosolic splicing variant of NELL2 inhibits PKCβ1 in glial cells.
abstract: NELL2 is an abundant glycoprotein containing EGF-like domain in the neural tissues where it has multiple physiological functions by interacting with protein kinase C (PKC). There are two different splicing variant forms of NELL2 identified so far. One is secreted NELL2 (sNELL2) which is a neuron-specific variant and the other is cytosolic NELL2 (cNELL2) which is non-secreted splicing variant of NELL2. Although cNELL2 structure was well characterized, the expression pattern or the cellular function of cNELL2 is not fully determined. In this study, we found that cNELL2 specifically interacts with PKCβ isotypes and inhibits PKCβ1 through direct binding to the N-terminal pseudosubstrate domain of PKCβ1. Here, we also demonstrate that cNELL2 is predominantly expressed and has inhibitory effects on the PKC downstream signaling pathways in astrocytes thereby establishing cNELL2 as an endogenous inhibitor of PKCβ1 in glia.
authors.affiliation: Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Da Yong
authors.initials: da Y
authors.lastname: Lee
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Kim
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Hwani
authors.initials: H
authors.lastname: Ryu
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-703, Republic of Korea. Electronic address: jaeyong68@Korea.ac.kr.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea; Neuroscience Program, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea. Electronic address: emhwang@kist.re.kr.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D016466:CHO Cells; D002478:Cells, Cultured; D003412:Cricetulus; D003600:Cytosol / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D064546:Protein Kinase C beta / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C491253:Nell2 protein, mouse; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D064546:Protein Kinase C beta
keywords: Astrocytes; Cytosolic NELL2; NELL2; PKCβ1; Pseudosubstrate domain