Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor.
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Bagowski CP, Stein-Gerlach M, Choidas A, Ullrich A
Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor.
EMBO J. 1999 Oct 15;18(20):5567-76.
- PubMed ID
- 10523301 [ View in PubMed]
- Abstract
In Rat-1 fibroblasts epidermal growth factor (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.