PMID- 10523301
OWN - NLM
STAT- MEDLINE
DCOM- 19991206
LR  - 20181201
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 20
DP  - 1999 Oct 15
TI  - Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the
      signal capacity of the EGF receptor.
PG  - 5567-76
AB  - 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.
FAU - Bagowski, C P
AU  - Bagowski CP
AD  - Department of Molecular Biology, Max-Planck-Institute for Biochemistry, Am
      Klopferspitz 18A, 82152 Martinsried, Germany.
FAU - Stein-Gerlach, M
AU  - Stein-Gerlach M
FAU - Choidas, A
AU  - Choidas A
FAU - Ullrich, A
AU  - Ullrich A
LA  - eng
PT  - Journal Article
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (RNA, Messenger)
RN  - 2ZD004190S (Threonine)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.- (protein kinase D)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Line
MH  - DNA/biosynthesis
MH  - Enzyme Activation/drug effects
MH  - Epidermal Growth Factor/pharmacology
MH  - ErbB Receptors/chemistry/genetics/*metabolism
MH  - Genes, fos
MH  - Genes, jun
MH  - Humans
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Protein Kinase C/*metabolism
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Receptor Cross-Talk
MH  - Signal Transduction
MH  - Threonine/*metabolism
PMC - PMC1171625
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1093/emboj/18.20.5567 [doi]
PST - ppublish
SO  - EMBO J. 1999 Oct 15;18(20):5567-76. doi: 10.1093/emboj/18.20.5567.