A joint project of the Graduate School, Peabody College, and the Jean & Alexander Heard Library

Title page for ETD etd-01302006-133128


Type of Document Dissertation
Author Henage, Lee Gardner
URN etd-01302006-133128
Title Kinetic analysis of phospholipase D: Allosteric modulation by monomeric GTPases, protein kinase C, and polyphosphoinositides
Degree PhD
Department Pharmacology
Advisory Committee
Advisor Name Title
Vsevolod V. Gurevich Committee Chair
Albert H. Beth Committee Member
H. Alex Brown Committee Member
Heidi E. Hamm Committee Member
John H. Exton Committee Member
Terry R. Lybrand Committee Member
Keywords
  • phospholipase d
  • enzymology
  • G-protein
  • protein kinase C
  • ADP-ribosylation factor
Date of Defense 2006-01-11
Availability unrestricted
Abstract
In mammalian cells, phospholipase D activity is tightly regulated by diverse cellular signals including hormones, neurotransmitters, and growth factors. Multiple signaling pathways converge upon phospholipase D to modulate cellular actions such as cell growth, shape and secretion. The kinetic properties of protein kinase C and G-protein regulation of mammalian phospholipase D1 (PLD1) were examined in order to better understand interactions between PLD1 and its regulators. Activation by Arf-1, RhoA, Rac1, Cdc42, protein kinase Ca, and phosphatidylinositol 4,5-bisphosphate displayed surface dilution kinetics, but these effectors modulated different kinetic parameters. A kinetic description of PLD1 activation by multiple modulators reveals a mechanism for apparent synergy between activators. These findings suggest a role for PLD1 as a signaling node, in which integration of convergent signals occurs within discrete locales of the cellular membrane.
Files
  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  LGHDissertation2006.pdf 12.18 Mb 00:56:23 00:29:00 00:25:22 00:12:41 00:01:04

Browse All Available ETDs by ( Author | Department )

If you have more questions or technical problems, please Contact LITS.