Loading...
Role of Protein Kinase C delta in regulating platelet functional responses
Bhavanasi, Dheeraj
Bhavanasi, Dheeraj
Citations
Altmetric:
Genre
Thesis/Dissertation
Date
2014
Advisor
Committee member
Group
Department
Physiology
Subject
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
http://dx.doi.org/10.34944/dspace/2583
Abstract
Platelets upon activation change their shape, aggregate and secrete alpha and dense granule contents among which ADP acts as a feedback activator. Different Protein Kinase C (PKCĪ“) isoforms have specific non-redundant roles in mediating platelet responses including secretion and thrombus formation. Protein Kinase C delta (PKCĪ“), a novel class of PKC isoform requiring diacyl glycerol but not calcium for its activation, has been shown to play an important role in several pathological processes. The aims of our current study are 1) to identify possible PKCĪ“ specific substrates in platelets, 2) evaluate a novel PKCĪ“ selective inhibitor and 3) to investigate the role of PKCĪ“ in ADP-induced platelet activation. We show that Protein kinase D2 (PKD2) is the major isoform of PKD that is expressed in human as well as murine platelets and is a specific substrate for PKCĪ“ in platelets. CGX1037 was identified and characterized as a selective small molecule inhibitor of PKCĪ“ in platelets. Furthermore, by using PKCĪ“ knock out murine platelets, we showed that PKCĪ“ plays a functional role in mediating ADP-induced thromboxane generation and classical PKC isoforms Ī±/Ī² regulate tyrosine phosphorylation on PKCĪ“ and subsequent thromboxane generation through a tyrosine kinase, Lyn and a tyrosine phosphatase, Shp1 suggesting an important role of PKCĪ“ to agonist-induced platelet activation.
Description
Citation
Citation to related work
Has part
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu