Membrane Binding Kinetics of Protein Kinase C βII Mediated by the C2 Domain†

Biochemistry ◽  
2001 ◽  
Vol 40 (44) ◽  
pp. 13216-13229 ◽  
Author(s):  
Eric A. Nalefski ◽  
Alexandra C. Newton
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Membrane Binding ◽  
Binding Kinetics ◽  
C2 Domain ◽  
Kinase C ◽  
Kinetics Of

scholarly journals Physiological Role for Phosphatidic Acid in the Translocation of the Novel Protein Kinase C Apl II in Aplysia Neurons

2008 ◽  
Vol 28 (15) ◽  
pp. 4719-4733 ◽  
Author(s):  
Carole A. Farah ◽  
Ikue Nagakura ◽  
Daniel Weatherill ◽  
Xiaotang Fan ◽  
Wayne S. Sossin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidic Acid ◽  
Physiological Role ◽  
C2 Domain ◽  
The Novel ◽  
Physiological Conditions ◽  
Kinase C ◽  
Neuronal Membranes ◽  
Novel Protein

ABSTRACT In Aplysia californica, the serotonin-mediated translocation of protein kinase C (PKC) Apl II to neuronal membranes is important for synaptic plasticity. The orthologue of PKC Apl II, PKCε, has been reported to require phosphatidic acid (PA) in conjunction with diacylglycerol (DAG) for translocation. We find that PKC Apl II can be synergistically translocated to membranes by the combination of DAG and PA. We identify a mutation in the C1b domain (arginine 273 to histidine; PKC Apl II-R273H) that removes the effects of exogenous PA. In Aplysia neurons, the inhibition of endogenous PA production by 1-butanol inhibited the physiological translocation of PKC Apl II by serotonin in the cell body and at the synapse but not the translocation of PKC Apl II-R273H. The translocation of PKC Apl II-R273H in the absence of PA was explained by two additional effects of this mutation: (i) the mutation removed C2 domain-mediated inhibition, and (ii) the mutation decreased the concentration of DAG required for PKC Apl II translocation. We present a model in which, under physiological conditions, PA is important to activate the novel PKC Apl II both by synergizing with DAG and removing C2 domain-mediated inhibition.

scholarly journals The C2 Domain and Altered ATP-Binding Loop Phosphorylation at Ser359Mediate the Redox-Dependent Increase in Protein Kinase C-δ Activity

2015 ◽  
Vol 35 (10) ◽  
pp. 1727-1740 ◽  
Author(s):  
Jianli Gong ◽  
Yongneng Yao ◽  
Pingbo Zhang ◽  
Barath Udayasuryan ◽  
Elena V. Komissarova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Domain ◽  
Cellular Growth ◽  
C2 Domain ◽  
Kinase C ◽  
High Level ◽  
Docking Interaction ◽  
Structural Determinant

The diverse roles of protein kinase C-δ (PKCδ) in cellular growth, survival, and injury have been attributed to stimulus-specific differences in PKCδ signaling responses. PKCδ exerts membrane-delimited actions in cells activated by agonists that stimulate phosphoinositide hydrolysis. PKCδ is released from membranes as a Tyr313-phosphorylated enzyme that displays a high level of lipid-independent activity and altered substrate specificity during oxidative stress. This study identifies an interaction between PKCδ's Tyr313-phosphorylated hinge region and its phosphotyrosine-binding C2 domain that controls PKCδ's enzymology indirectly by decreasing phosphorylation in the kinase domain ATP-positioning loop at Ser359. We show that wild-type (WT) PKCδ displays a strong preference for substrates with serine as the phosphoacceptor residue at the active site when it harbors phosphomimetic or bulky substitutions at Ser359.In contrast, PKCδ-S359A displays lipid-independent activity toward substrates with either a serine or threonine as the phosphoacceptor residue. Additional studies in cardiomyocytes show that oxidative stress decreases Ser359phosphorylation on native PKCδ and that PKCδ-S359A overexpression increases basal levels of phosphorylation on substrates with both phosphoacceptor site serine and threonine residues. Collectively, these studies identify a C2 domain-pTyr313docking interaction that controls ATP-positioning loop phosphorylation as a novel, dynamically regulated, and physiologically relevant structural determinant of PKCδ catalytic activity.

Structure of human protein kinase C eta (PKCη) C2 domain and identification of phosphorylation sites

2006 ◽  
Vol 349 (4) ◽  
pp. 1182-1189 ◽  
Author(s):  
Dene R. Littler ◽  
John R. Walker ◽  
Yi-Min She ◽  
Patrick J. Finerty ◽  
Elena M. Newman ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Human Protein ◽  
Phosphorylation Sites ◽  
C2 Domain ◽  
Kinase C ◽  
Human Protein Kinase

scholarly journals Crystal structure of the C2 domain from protein kinase C-δ

Structure ◽  
1998 ◽  
Vol 6 (7) ◽  
pp. 885-894 ◽  
Author(s):  
H Pappa ◽  
J Murray-Rust ◽  
LV Dekker ◽  
PJ Parker ◽  
NQ McDonald
Keyword(s):  
Crystal Structure ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
C2 Domain ◽  
Kinase C

scholarly journals Correlation between membrane binding and phosphorylation by protein kinase C of acylated protein.

1990 ◽  
Vol 54 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Toshihiko UTSUMI ◽  
Hiroshi KOFUJI ◽  
Keisuke EDASHIGE ◽  
Kozo UTSUMI ◽  
Daizo KOGA ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Membrane Binding ◽  
Kinase C

The kinetics of translocation and cellular quantity of protein kinase C in human leukocytes are modified during spaceflight

1999 ◽  
Vol 13 (9001) ◽  
Author(s):  
Jason P. Hatton ◽  
Francois Gaubert ◽  
Marian L. Lewis ◽  
Yann Darsel ◽  
Philippe Ohlmann ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Human Leukocytes ◽  
Kinase C ◽  
Kinetics Of

scholarly journals Delayed accumulation of diacylglycerol in platelets as a mechanism for regulation of onset of aggregation and secretion

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 435-444 ◽  
Author(s):  
MH Werner ◽  
YA Hannun
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Shape Change ◽  
Human Platelets ◽  
Optimal Timing ◽  
Delayed Effects ◽  
Kinase C ◽  
Irreversible Aggregation ◽  
Kinetics Of ◽  
Sustained Activation

Abstract An important mechanism of platelet regulation is the formation of the second messenger diacylglycerol (DAG) and the activation of protein kinase C (PKC). Our previous studies suggested that the DAG/PKC pathway plays an important role in the induction of secretion and secondary aggregation rather than the earlier events of shape change and primary aggregation. We therefore examined the hypothesis that the delayed effects of PKC on platelets may result from delayed accumulation of DAG. The kinetics of DAG formation in human platelets were determined. When platelets were stimulated with gamma-thrombin, the largest phase of DAG accumulation was delayed for 0.6 to 0.8 minutes and DAG mass levels remained elevated for at least 2 minutes. In platelets stimulated with collagen, DAG accumulation was delayed for 1.0 to 1.2 minutes and DAG mass levels remained elevated for at least 3 minutes after stimulation. Sustained DAG production was also associated with sustained activation of PKC as monitored by phosphorylation of the 40- Kd substrate of PKC. The physiologic significance of delayed DAG accumulation was investigated using the cell-permeable DAG analog, dioctanoylglycerol (diC8). In synergy with subthreshold gamma-thrombin or collagen, exogenous diC8 reconstituted platelet activation. The optimal timing of addition of diC8 was 0.5 minutes after stimulation with gamma-thrombin or collagen. These kinetics were similar to those of endogenous DAG accumulation. These studies underscore the importance of a delayed accumulative phase of DAG generation as a mechanism controlling the onset of platelet secretion and irreversible aggregation.

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