Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor
Open Access
- 15 October 1999
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 18 (20) , 5567-5576
- https://doi.org/10.1093/emboj/18.20.5567
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.Keywords
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