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

来源：

EMBO JOURNAL | 1999年 / 18卷 / 20期

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

页码：5567 / 5576

页数：10

共 57 条

[41] SIGNAL-TRANSDUCTION BY TUMOR-NECROSIS-FACTOR MEDIATED BY JNK PROTEIN-KINASES [J].

SLUSS, HK ;

BARRETT, T ;

DERIJARD, B ;

DAVIS, RJ .

MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (12) :8376-8384

[42] ONCOPROTEIN-MEDIATED SIGNALING CASCADE STIMULATES C-JUN ACTIVITY BY PHOSPHORYLATION OF SERINE-63 AND SERINE-73 [J].

SMEAL, T ;

BINETRUY, B ;

MERCOLA, D ;

GROVERBARDWICK, A ;

HEIDECKER, G ;

RAPP, UR ;

KARIN, M .

MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (08) :3507-3513

[43]

THEROUX SJ, 1992, J BIOL CHEM, V267, P7967

[44] Regulation of transcription by MAP kinase cascades [J].

Treisman, R .

CURRENT OPINION IN CELL BIOLOGY, 1996, 8 (02) :205-215

[45] HUMAN EPIDERMAL GROWTH-FACTOR RECEPTOR CDNA SEQUENCE AND ABERRANT EXPRESSION OF THE AMPLIFIED GENE IN A431 EPIDERMOID CARCINOMA-CELLS [J].

ULLRICH, A ;

COUSSENS, L ;

HAYFLICK, JS ;

DULL, TJ ;

GRAY, A ;

TAM, AW ;

LEE, J ;

YARDEN, Y ;

LIBERMANN, TA ;

SCHLESSINGER, J ;

DOWNWARD, J ;

MAYES, ELV ;

WHITTLE, N ;

WATERFIELD, MD ;

SEEBURG, PH .

NATURE, 1984, 309 (5967) :418-425

[46] MOLECULAR-CLONING AND CHARACTERIZATION OF PROTEIN-KINASE-D - A TARGET FOR DIACYLGLYCEROL AND PHORBOL ESTERS WITH A DISTINCTIVE CATALYTIC DOMAIN [J].

VALVERDE, AM ;

SINNETTSMITH, J ;

VANLINT, J ;

ROZENGURT, E .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (18) :8572-8576

[47] Platelet-derived growth factor stimulates protein kinase D through the activation of phospholipase Cγ and protein kinase C [J].

Van Lint, J ;

Ni, YP ;

Valius, M ;

Merlevede, W ;

Vandenheede, JR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (12) :7038-7043

[48] Selective cleavage of the heregulin receptor ErbB-4 by protein kinase C activation [J].

Vecchi, M ;

Baulida, J ;

Carpenter, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (31) :18989-18995

[49] HEREGULIN-DEPENDENT REGULATION OF HER2/NEU ONCOGENIC SIGNALING BY HETERODIMERIZATION WITH HER3 [J].

WALLASCH, C ;

WEISS, FU ;

NIEDERFELLNER, G ;

JALLAL, B ;

ISSING, W ;

ULLRICH, A .

EMBO JOURNAL, 1995, 14 (17) :4267-4275

[50] Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G(1) phase [J].

Weber, JD ;

Raben, DM ;

Phillips, PJ ;

Baldassare, JJ .

BIOCHEMICAL JOURNAL, 1997, 326 :61-68

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