Elucidating the interaction of γ-hydroxymethyl-γ-butyrolactone substituents with model membranes and protein kinase C–C1 domains

2015 ◽  
Vol 11 (5) ◽  
pp. 1389-1399
Author(s):  
Rituparna Borah ◽  
Narsimha Mamidi ◽  
Subhankar Panda ◽  
Sukhamoy Gorai ◽  
Suraj Kumar Pathak ◽  
...  

Investigation of γ-hydroxymethyl-γ-butyrolactone substituents as protein kinase C ligands, in an effort to develop small molecule-based regulators with higher specificity for C1 domain than the endogenous ligand, diacylglycerols.

2010 ◽  
Vol 21 (8) ◽  
pp. 1398-1408 ◽  
Author(s):  
HongBin Wang ◽  
Marcelo G. Kazanietz

The C1 domains in protein kinase C (PKC) isozymes and other signaling molecules are responsible for binding the lipid second messenger diacylglycerol and phorbol esters, and for mediating translocation to membranes. Previous studies revealed that the C1 domain in α- and β-chimaerins, diacylglycerol-regulated Rac-GAPs, interacts with the endoplasmic reticulum/Golgi protein p23/Tmp21. Here, we found that p23/Tmp21 acts as a C1 domain-docking protein that mediates perinuclear translocation of β2-chimaerin. Glu227 and Leu248 in the β2-chimaerin C1 domain are crucial for binding p23/Tmp21 and perinuclear targeting. Interestingly, isolated C1 domains from individual PKC isozymes differentially interact with p23/Tmp21. For PKCε, it interacts with p23/Tmp21 specifically via its C1b domain; however, this association is lost in response to phorbol esters. These results demonstrate that p23/Tmp21 acts as an anchor that distinctively modulates compartmentalization of C1 domain-containing proteins, and it plays an essential role in β2-chimaerin relocalization. Our study also highlights the relevance of C1 domains in protein–protein interactions in addition to their well-established lipid-binding properties.


2012 ◽  
Vol 165 (3) ◽  
pp. 320-330 ◽  
Author(s):  
Narsimha Mamidi ◽  
Sukhamoy Gorai ◽  
Jashobanta Sahoo ◽  
Debasis Manna

2018 ◽  
Vol 84 (3) ◽  
pp. 193-201 ◽  
Author(s):  
Angelo Blasio ◽  
Jingyi Wang ◽  
Dan Wang ◽  
Florence P. Varodayan ◽  
Matthew B. Pomrenze ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jessica Brogdon ◽  
Widade Ziani ◽  
Xiaolei Wang ◽  
Ronald S. Veazey ◽  
Huanbin Xu

1999 ◽  
Vol 372 (2) ◽  
pp. 382-388 ◽  
Author(s):  
Josefa García-García ◽  
Vicente Micol ◽  
Ana de Godos ◽  
Juan C. Gómez-Fernández

2005 ◽  
Vol 280 (29) ◽  
pp. 27329-27338 ◽  
Author(s):  
Yongmei Pu ◽  
Nicholas A. Perry ◽  
Dazhi Yang ◽  
Nancy E. Lewin ◽  
Noemi Kedei ◽  
...  

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