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Title: The PKCα-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals
Authors: Zhu, Y.
Dong, Q.
Tan, B.J. 
Lim, W.G.
Zhou, S. 
Duan, W.
Issue Date: 1-Jun-2005
Source: Zhu, Y., Dong, Q., Tan, B.J., Lim, W.G., Zhou, S., Duan, W. (2005-06-01). The PKCα-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals. Cancer Research 65 (11) : 4520-4524. ScholarBank@NUS Repository.
Abstract: 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. © 2005 American Association for Cancer Research.
Source Title: Cancer Research
ISSN: 00085472
DOI: 10.1158/0008-5472.CAN-04-4506
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