Calphostin C, a widely used protein kinase C inhibitor, directly and potently blocks L-type Ca channels

1996 ◽  
Vol 270 (5) ◽  
pp. C1293-C1299 ◽  
Author(s):  
H. C. Hartzell ◽  
A. Rinderknecht
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Selective Inhibitor ◽  
Ca Channels ◽  
Ca Current ◽  
The Past ◽  
Calphostin C ◽  
Kinase C ◽  
Voltage Dependent ◽  
Protein Kinase C Inhibitor

Calphostin C is a widely used inhibitor of protein kinase C; in the past 4 years at least 350 articles have been published using this drug as a selective inhibitor of protein kinase C. In this paper, we show that calphostin C also potently inhibits cardiac L-type Ca channels by a mechanism that does not involve changes in adenosine 3',5'-cyclic monophosphate levels or dephosphorylation. The inhibition requires illumination by visible light during exposure to calphostin C. The Ca current (ICa) that remains after partial inhibition of ICa has the same voltage-dependent characteristics as the control current.

Protein-kinase-C inhibitor calphostin C reduces B16 amelanotic melanoma cell adhesion to endothelium and lung colonization

1992 ◽  
Vol 52 (1) ◽  
pp. 147-152 ◽  
Author(s):  
Bin Liu ◽  
Colette Renaud ◽  
Kevin K. Nelson ◽  
Yong Q. Chen ◽  
Rajesh Bazaz ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Melanoma Cell ◽  
Amelanotic Melanoma ◽  
Calphostin C ◽  
Kinase C ◽  
Lung Colonization ◽  
Protein Kinase C Inhibitor

scholarly journals Inhibition of voltage-dependent sodium channels by Ro 31-8220, a ‘specific’ protein kinase C inhibitor

FEBS Letters ◽  
2000 ◽  
Vol 473 (2) ◽  
pp. 265-268 ◽  
Author(s):  
Ratnakumari Lingameneni ◽  
Tanya N. Vysotskaya ◽  
Daniel S. Duch ◽  
Hugh C. Hemmings
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Sodium Channels ◽  
Specific Protein ◽  
Kinase C ◽  
Voltage Dependent ◽  
Protein Kinase C Inhibitor ◽  
Specific Protein Kinase

scholarly journals The Small Mr Ras-like GTPase Rap1 and the Phospholipase C Pathway Act to Regulate Phagocytosis inDictyostelium discoideum

1999 ◽  
Vol 10 (2) ◽  
pp. 393-406 ◽  
Author(s):  
David J. Seastone ◽  
Linyi Zhang ◽  
Greg Buczynski ◽  
Patrick Rebstein ◽  
Gerald Weeks ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Protein Tyrosine Kinase ◽  
Dominant Negative ◽  
Wild Type ◽  
Cortical Actin ◽  
Calphostin C ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

The function of the small-Mr Ras-like GTPase Rap1 remains largely unknown, but this protein has been demonstrated to regulate cortical actin-based morphologic changes inDictyostelium and the oxidative burst in mammalian neutrophils. To test whether Rap1 regulates phagocytosis, we biochemically analyzed cell lines that conditionally and modestly overexpressed wild-type [Rap1 WT(+)], constitutively active [Rap1 G12T(+)], and dominant negative [Rap1 S17N(+)] forms of D. discoideum Rap1. The rates of phagocytosis of bacteria and latex beads were significantly higher in Rap1 WT(+) and Rap1 G12T(+) cells and were reduced in Rap1 S17N(+) cells. The addition of inhibitors of protein kinase A, protein kinase G, protein tyrosine kinase, or phosphatidylinositide 3-kinase did not affect phagocytosis rates in wild-type cells. In contrast, the addition of U73122 (a phospholipase C inhibitor), calphostin C (a protein kinase C inhibitor), and BAPTA-AM (an intracellular Ca2+ chelator) reduced phagocytosis rates by 90, 50, and 65%, respectively, suggesting both arms of the phospholipase C signaling pathways played a role in this process. Other protein kinase C–specific inhibitors, such as chelerythrine and bisindolylmaleimide I, did not reduce phagocytosis rates in control cells, suggesting calphostin C was affecting phagocytosis by interfering with a protein containing a diacylglycerol-binding domain. The addition of calphostin C did not reduce phagocytosis rates in Rap1 G12T(+) cells, suggesting that the putative diacylglycerol-binding protein acted upstream in a signaling pathway with Rap1. Surprisingly, macropinocytosis was significantly reduced in Rap1 WT(+) and Rap1 G12T(+) cells compared with control cells. Together our results suggest that Rap1 and Ca2+ may act together to coordinate important early events regulating phagocytosis.

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