scholarly journals Diacylglycerol kinase is phosphorylated in vivo upon stimulation of the epidermal growth factor receptor and serine/threonine kinases, including protein kinase C-ε

1993 ◽  
Vol 289 (3) ◽  
pp. 875-881 ◽  
Author(s):  
D Schaap ◽  
J van der Wal ◽  
W J van Blitterswijk ◽  
R L van der Bend ◽  
H L Ploegh
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Kinase C ◽  
Pkc Epsilon ◽  
Epidermal Growth

In signal transduction, diacylglycerol (DG) kinase attenuates levels of the second messenger DG by converting it to phosphatidic acid. A previously cloned full-length human 86 kDa DG kinase cDNA was expressed as fusion protein in Escherichia coli, to aid in the generation of DG-kinase-specific monoclonal antibodies suitable for immunoprecipitation experiments. To investigate whether phosphorylation of DG kinase is a possible mechanism for its regulation, COS-7 cells were transiently transfected with the DG kinase cDNA and phosphorylation of the expressed DG kinase was induced by various stimuli. Activation of both cyclic AMP-dependent protein kinase and protein kinase C (PKC) resulted in phosphorylation of DG kinase on serine residues in vivo, and both kinases induced this phosphorylation within the same tryptic phosphopeptide, suggesting that they may exert similar control over DG kinase. No phosphorylation was observed upon ionomycin treatment, intended to activate Ca2+/calmodulin-dependent kinases. Co-transfections of DG kinase with either PKC-alpha or PKC-epsilon cDNA revealed that both protein kinases, when stimulated, are able to phosphorylate DG kinase. For PKC-epsilon, DG kinase is the first in vivo substrate identified. Stimulation with epidermal growth factor (EGF) of COS-7 cells transfected with both DG kinase and EGF-receptor cDNA results mainly in phosphorylation of DG kinase on tyrosine. Since the EGF receptor has an intrinsic tyrosine kinase activity, this finding implies that DG kinase may be a direct substrate for the activated EGF receptor.

scholarly journals Epidermal Growth Factor Receptor and Protein Kinase C Signaling to ERK2

2008 ◽  
Vol 283 (10) ◽  
pp. 6241-6252 ◽  
Author(s):  
Christopher J. Caunt ◽  
Caroline A. Rivers ◽  
Becky L. Conway-Campbell ◽  
Michael R. Norman ◽  
Craig A. McArdle
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Kinase C ◽  
Epidermal Growth

scholarly journals Rapid stimulation of amyloid precursor protein release by epidermal growth factor: role of protein kinase C

1997 ◽  
Vol 327 (1) ◽  
pp. 245-249 ◽  
Author(s):  
Barbara E. SLACK ◽  
Jeffrey BREU ◽  
Lisa MUCHNICKI ◽  
Richard J. WURTMAN
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Amyloid Precursor Protein ◽  
Egf Receptor ◽  
A431 Cells ◽  
Kinase C ◽  
Epidermal Growth ◽  
Stimulation Of

The amyloid precursor protein (APP) of Alzheimer's disease is a transmembrane protein that is cleaved by an uncharacterized enzyme known as α-secretase within its extracellular/intraluminal domain after the activation of guanine nucleotide-binding protein-coupled receptors linked to phosphoinositide hydrolysis. The secretory process results in the release of large soluble derivatives of APP (APPs), and, when elicited by muscarinic receptor activation, exhibits both protein kinase C (PKC)-dependent and tyrosine phosphorylation-dependent components [Slack, Breu, Petryniak, Srivastava and Wurtman (1995) J. Biol. Chem. 270, 8337–8344]. In this report we examine the regulation of the release of APPs by epidermal growth factor (EGF) receptors, which possess intrinsic tyrosine kinase activity, and are coupled to a variety of effectors including phosphoinositide-specific phospholipase Cγ. In A431 cells, EGF caused time-dependent and dose-dependent increases in the formation of inositol phosphates in cultures prelabelled with myo-[3H]inositol, and in the release of APPs into the culture medium; the two responses exhibited similar time courses and EC50 values for EGF. Concomitant with these effects, there were concentration-dependent (3–300 ng/ml) increases in the phosphorylation of tyrosine residues in several proteins, including the EGF receptor itself. The specific PKC antagonist GF 109203X decreased the effect of EGF by approx. 35% at a concentration that abolished the stimulation of the release of APPs by the PKC activator PMA. Tyrphostin AG 1478, an inhibitor of EGF receptor tyrosine kinase, abolished the EGF-induced release of APPs. These results demonstrate that in A431 cells, activation of the EGF receptor stimulates α-secretase activity by a mechanism that is partly dependent on PKC activity.

scholarly journals Sustained Activation of Protein Kinase C Induces Delayed Phosphorylation and Regulates the Fate of Epidermal Growth Factor Receptor

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80721 ◽  
Author(s):  
Mengling Liu ◽  
Jolanta Idkowiak-Baldys ◽  
Patrick L. Roddy ◽  
Aleksander Baldys ◽  
John Raymond ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Kinase C ◽  
Epidermal Growth ◽  
Sustained Activation
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