Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor

被引:74
作者
Bagowski, CP [1 ]
Stein-Gerlach, M [1 ]
Choidas, A [1 ]
Ullrich, A [1 ]
机构
[1] Max Planck Inst Biochem, Dept Mol Biol, D-82152 Martinsried, Germany
关键词
c-Jun N-terminal kinase; epidermal growth factor receptor; platelet-derived growth factor receptor; protein kinase D; threonine phosphorylation;
D O I
10.1093/emboj/18.20.5567
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
In Rat-1 fibroblasts epidermal growth fatter (EGF), but not platelet-derived growth factor (PDGF) stimulates the activity of the c-Jun N-terminal kinase (JNK), Moreover, PDGF induced suppression of EGF-mediated JNK activation, apparently through protein kinase C (PKC) activation. Further analysis revealed that PKD was specifically activated by PDGF but not EGF in Rat-1 cells. In SF126 glioblastoma cells, however, EGF and PDGF synergistically activated JNK, while neither PDGF nor EGF stimulated PKD activity. In this cell line, overexpression of PKD blocked EGF- and PDGF-induced JNK activation. Mutational analysis further revealed that the EGFR mutant (T654/669E) was incapable of activating JNK and provided evidence that PKD-mediated dual phosphorylation of these critical threonine residues leads to suppression of EGF-induced JNK activation. Our results establish a novel crosstalk mechanism which allows signal integration and definition in cells with many different RTKs.
引用
收藏
页码:5567 / 5576
页数:10
相关论文
共 57 条
[1]   EGF or PDGF receptors activate atypical PKC lambda through phosphatidylinositol 3-kinase [J].
Akimoto, K ;
Takahashi, R ;
Moriya, S ;
Nishioka, N ;
Takayanagi, J ;
Kimura, K ;
Fukui, Y ;
Osada, S ;
Mizuno, K ;
Hirai, S ;
Kazlauskas, A ;
Ohno, S .
EMBO JOURNAL, 1996, 15 (04) :788-798
[2]   THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION [J].
ANGEL, P ;
KARIN, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) :129-157
[3]   Constitutive activation of c-Jun N-terminal kinase by a mutant epidermal growth factor receptor [J].
Antonyak, MA ;
Moscatello, DK ;
Wong, AJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (05) :2817-2822
[4]   The JUN kinase stress-activated protein kinase pathway is required for epidermal growth factor stimulation of growth of human A549 lung carcinoma cells [J].
Bost, F ;
McKay, R ;
Dean, N ;
Mercola, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (52) :33422-33429
[5]   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
[6]   PARALLEL SIGNAL-PROCESSING AMONG MAMMALIAN MAPKS [J].
CANO, E ;
MAHADEVAN, LC .
TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (03) :117-122
[7]  
CLEMENS MJ, 1992, J CELL SCI, V103, P881
[8]  
COLLINS MKL, 1983, J BIOL CHEM, V258, P1689
[9]  
COUNTAWAY JL, 1992, J BIOL CHEM, V267, P1129
[10]  
COUNTAWAY JL, 1989, J BIOL CHEM, V264, P10828