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

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