Protein kinase C (PKC) η-mediated PKCμ activation modulates ERK and JNK signal pathways

被引:116
作者
Brändlin, I
Hübner, S
Eiseler, T
Martinez-Moya, M
Horschinek, A
Hausser, A
Link, G
Rupp, S
Storz, P
Pfizenmaier, K
Johannes, FJ
机构
[1] Fraunhofer Inst Interfacial Engn, D-70569 Stuttgart, Germany
[2] Univ Stuttgart, Inst Cell Biol & Immunol, D-70569 Stuttgart, Germany
[3] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA
关键词
D O I
10.1074/jbc.M106083200
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
Protein kinase C (PKC), a family of lipid-activated serine kinases, is involved in multiple functions in the regulation of growth control. The PKC-related isoform PKCmu/PKD has been implicated in mitogenic signal cascades because of the activation of p42/p44 MAPK leading to Elk1-mediated gene transcription, and PKCmu/PKD has been shown to be activated via a PKC-dependent pathway. By using confocal analyses, we demonstrate here that PKCmu partially colocalizes with PKC-eta in different cell types. Colocalization depends on the presence of the PKCmu pleckstrin homology domain. Coexpression of constitutively active PKC-eta with PKCmu leads to a significant enhancement of the PKCmu substrate phosphorylation capacity as a result of an increased phosphorylation of the activation loop Ser(738/742) of PKCmu, whereas Ser(910) autophosphorylation remains unaffected. In vitro phosphorylation experiments show that PKCeta directly phosphorylates PKCmu on activation loop serines. Consequently, the p42 MAPK cascade is triggered leading to an increase in reporter gene activity driven by a serum-responsive element in HEK293 cells. At the same time, PKCeta-mediated JNK activation is reduced, providing evidence for a mutual regulation of PKCmu/PKCeta affecting different arms of the p38/ERK/ JNK pathways. Our data provide evidence for the sequential involvement of selective PKC isoforms in kinase cascades and identify the relevant domains in PKCmu for interaction with and activation by PKCeta as pleckstrin homology domain and activation loop.
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页码:6490 / 6496
页数:7
相关论文
共 38 条
[1]   Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor [J].
Bagowski, CP ;
Stein-Gerlach, M ;
Choidas, A ;
Ullrich, A .
EMBO JOURNAL, 1999, 18 (20) :5567-5576
[2]   Protein kinase C-mediated regulation of the cell cycle [J].
Black, JD .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2000, 5 :D406-D423
[3]   Differential regulation of extracellular signal-regulated protein kinase 1 and Jun N-terminal kinase 1 by Ca2+ and protein kinase C in endothelin-stimutated Rat-1 cells [J].
Cadwallader, K ;
Beltman, J ;
McCormick, F ;
Cook, S .
BIOCHEMICAL JOURNAL, 1997, 321 :795-804
[4]   THE ETA-ISOFORM OF PROTEIN-KINASE-C IS LOCALIZED ON ROUGH ENDOPLASMIC-RETICULUM [J].
CHIDA, K ;
SAGARA, H ;
SUZUKI, Y ;
MURAKAMI, A ;
OSADA, SI ;
OHNO, S ;
HIROSAWA, K ;
KUROKI, T .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (06) :3782-3790
[5]   Regulation of protein kinase C ζ by PI 3-kinase and PDK-1 [J].
Chou, MM ;
Hou, WM ;
Johnson, J ;
Graham, LK ;
Lee, MH ;
Chen, CS ;
Newton, AC ;
Schaffhausen, BS ;
Toker, A .
CURRENT BIOLOGY, 1998, 8 (19) :1069-1077
[6]   In vitro activation and substrates of recombinant, baculovirus expressed human protein kinase C mu [J].
Dieterich, S ;
Herget, T ;
Link, G ;
Bottinger, H ;
Pfizenmaier, K ;
Johannes, FJ .
FEBS LETTERS, 1996, 381 (03) :183-187
[7]   Regulation of conventional protein kinase C isozymes by phosphoinositide-dependent kinase 1 (PDK-1) [J].
Dutil, EM ;
Toker, A ;
Newton, AC .
CURRENT BIOLOGY, 1998, 8 (25) :1366-1375
[8]   PH DOMAIN - THE FIRST ANNIVERSARY [J].
GIBSON, TJ ;
HYVONEN, M ;
MUSACCHIO, A ;
SARASTE, M ;
BIRNEY, E .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (09) :349-353
[9]   Regulation of protein kinase C mu by basic peptides and heparin - Putative role of an acidic domain in the activation of the kinase [J].
Gschwendt, M ;
Johannes, FJ ;
Kittstein, W ;
Marks, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20742-20746
[10]   Protein kinase C μ is negatively regulated by 14-3-3 signal transduction proteins [J].
Hausser, A ;
Storz, P ;
Link, G ;
Stoll, H ;
Liu, YC ;
Altman, A ;
Pfizenmaier, K ;
Johannes, FJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (14) :9258-9264