The PKCÁ-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals

Zhu, Yimin, Dong, Qihan, Tan, Bee Jen, Lim, Wee Guan, Zhou, Shufeng and Duan, Wei 2005, The PKCÁ-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals, Cancer research, vol. 65, no. 11, pp. 4520-4524.

Attached Files
Name Description MIMEType Size Downloads

Title The PKCÁ-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals
Formatted title PKCα-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals
Author(s) Zhu, Yimin
Dong, Qihan
Tan, Bee Jen
Lim, Wee Guan
Zhou, Shufeng
Duan, Wei
Journal name Cancer research
Volume number 65
Issue number 11
Start page 4520
End page 4524
Publisher American Association for Cancer Research
Place of publication Philadelphia, Pa.
Publication date 2005-06-01
ISSN 0008-5472
Summary Protein kinase C (PKC) is a key regulator of cell proliferation, differentiation, and apoptosis and is one of the drug targets of anticancer therapy. Recently, a single point mutation (D294G) in PKCα has been found in pituitary and thyroid tumors with more invasive phenotype. Although the PKCα-D294G mutant is implicated in the progression of endocrine tumors, no apparent biochemical/cell biological abnormalities underlying tumorigenesis with this mutant have been found. We report here that the PKCα-D294G mutant is unable to bind to cellular membranes tightly despite the fact that it translocates to the membrane as efficiently as the wild-type PKCα upon treatment of phorbol ester. The impaired membrane binding is associated with this mutant's inability to transduce several antitumorigenic signals as it fails to mediate phorbol ester–stimulated translocation of myristoylated alanine–rich protein kinase C substrate (MARCKS), to activate mitogen-activated protein kinase and to augment melatonin-stimulated neurite outgrowth. Thus, the PKCα-D294G is a loss-of-function mutation. We propose that the wild-type PKCα may play important antitumorigenic roles in the progression of endocrine tumors. Therefore, developing selective activators instead of inhibitors of PKCα might provide effective pharmacological interventions for the treatment of certain endocrine tumors.
Language eng
Field of Research 060111 Signal Transduction
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2005, American Association for Cancer Research
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006555

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: Scopus Citation Count Cited 14 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 397 Abstract Views, 0 File Downloads  -  Detailed Statistics
Created: Thu, 31 Jul 2008, 10:41:47 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.