Identification of PKCζII:: an endogenous inhibitor of cell polarity

被引:24
作者
Parkinson, SJ [1 ]
Le Good, JA [1 ]
Whelan, RDH [1 ]
Whitehead, P [1 ]
Parker, PJ [1 ]
机构
[1] London Res Inst, Canc Res UK, Prot Phosphorylat Lab, London WC2A 3PX, England
关键词
cell polarity; Par6; PKC; RNAi; tight junction;
D O I
10.1038/sj.emboj.7600023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A new member of the atypical protein kinase C ( aPKC) family, designated PKCzetaII, is identified in this study. The gene contains no introns and is 98% homologous with the cDNA encoding PKCzeta. The PKCzetaII coding region is frame-shifted with respect to the PKCzeta open reading frame, resulting in expression of an aPKC regulatory domain without associated kinase activity. PKCzetaII mRNA is detected in various mouse tissues and an immunoreactive 45 kDa protein is present in epithelial cell cultures. PKCzetaII is shown to interact with the Par6 protein and functions in the development of cell polarity. HC11 epithelial cells express PKCzetaII and are maintained in a nondifferentiated state characterised by the absence of tight junctions and cell overgrowth. HC11 cells harbouring a PKCzetaII-specific RNAi, recruit ZO-1 and other tight junction markers to cell - cell boundaries and adopt a monolayer phenotype in the presence of growth factors. The data demonstrate a regulatory role for PKCzetaII in the maintenance of cell transformation and the development of cell polarity.
引用
收藏
页码:77 / 88
页数:12
相关论文
共 28 条
[11]   Positional cloning of heart and soul reveals multiple roles for PKCλ in zebrafish organogenesis [J].
Horne-Badovinac, S ;
Lin, D ;
Waldron, S ;
Schwarz, M ;
Mbamalu, G ;
Pawson, T ;
Jan, YN ;
Stainier, DYR ;
Abdelilah-Seyfried, S .
CURRENT BIOLOGY, 2001, 11 (19) :1492-1502
[12]   Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2 and ZO-3, with the COOH termini of claudins [J].
Itoh, M ;
Furuse, M ;
Morita, K ;
Kubota, K ;
Saitou, M ;
Tsukita, S .
JOURNAL OF CELL BIOLOGY, 1999, 147 (06) :1351-1363
[13]   The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42 [J].
Joberty, G ;
Petersen, C ;
Gao, L ;
Macara, IG .
NATURE CELL BIOLOGY, 2000, 2 (08) :531-539
[14]   X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif [J].
Kostrewa, D ;
Brockhaus, M ;
D'Arcy, A ;
Dale, GE ;
Nelboeck, P ;
Schmid, G ;
Mueller, F ;
Bazzoni, G ;
Dejana, E ;
Bartfai, T ;
Winkler, FK ;
Hennig, M .
EMBO JOURNAL, 2001, 20 (16) :4391-4398
[15]   A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity [J].
Lin, D ;
Edwards, AS ;
Fawcett, JP ;
Mbamalu, G ;
Scott, JD ;
Pawson, T .
NATURE CELL BIOLOGY, 2000, 2 (08) :540-547
[16]  
Liu Y, 2000, J CELL SCI, V113, P2363
[17]   Rat protein kinase C zeta gene contains alternative promoters for generation of dual transcripts with 5′-end heterogeneity [J].
Marshall, BS ;
Price, G ;
Powell, CT .
DNA AND CELL BIOLOGY, 2000, 19 (12) :707-719
[18]   The atypical protein kinase Cs - Functional specificity mediated by specific protein adapters [J].
Moscat, J ;
Diaz-Meco, MT .
EMBO REPORTS, 2000, 1 (05) :399-403
[19]  
Osten P, 1996, J NEUROSCI, V16, P2444
[20]   Nuclear import and export signals enable rapid nucleocytoplasmic shuttling of the atypical protein kinase C λ [J].
Perander, M ;
Bjorkoy, G ;
Johansen, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (16) :13015-13024