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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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AHNAK-mediated activation of phospholipase C-gamma 1 through protein kinase C

Cited 25 times inthomson ciCited 23 times inthomson ci
Title
AHNAK-mediated activation of phospholipase C-gamma 1 through protein kinase C
Author
Lee, IHYou, JOHa, KSBae, DSSuh, Pann-GhillRhee, SGBae, YS
Keywords
ARACHIDONIC-ACID RELEASE; A(2); CA2+; PHOSPHORYLATION; BRADYKININ; CALCIUM; GAMMA; CELLS; PLC-GAMMA-1; FIBROBLASTS
Issue Date
200406
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.279, no.25, pp.26645 - 26653
Abstract
We have recently shown that phospholipase C-gamma (PLC-gamma) is activated by the central repeated units ( CRUs) of the AHNAK protein in the presence of arachidonic acid. Here we demonstrate that four central repeated units ( 4 CRUs) of AHNAK act as a scaffolding motif networking PLC-gamma and PKC-alpha. Specifically, 4 CRUs of AHNAK bind and activate PKC-alpha, which in turn stimulates the release of arachidonic acid near where PLC-gamma1 is localized. Moreover, 4 CRUs of AHNAK interacted with PLC-gamma and the concerted action of 4 CRUs with arachidonic acid stimulated PLC-gamma activity. Stimulation of NIH3T3 cells expressing 4 CRUs of AHNAK with phorbol 12-myristate 13-acetate resulted in the increased generation of total inositol phosphates (IPT) and mobilization of the intracellular calcium. Phorbol 12-myristate 13-acetate-dependent generation of IPT was completely blocked in NIH3T3 cells depleted of PLC-gamma1 by RNA interference. Furthermore, bradykinin, which normally stimulated the PLC-beta isozyme resulting in the generation of a monophasic IPT within 30 s in NIH3T3 cells, led to a biphasic pattern for generation of IPT in NIH3T3 cells expressing 4 CRUs of AHNAK. The secondary activation of PLC is likely because of the scaffolding activity of AHNAK, which is consistent with the role of 4 CRUs as a molecular linker between PLC-gamma and PKC-alpha.
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DOI
http://dx.doi.org/10.1074/jbc.M311525200
ISSN
0021-9258
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