BROWSE

Related Researcher

Author

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

ITEM VIEW & DOWNLOAD

Interaction of elongation factor-1 alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity

Cited 31 times inthomson ciCited 31 times inthomson ci
Title
Interaction of elongation factor-1 alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity
Author
Chang, JSSeok, HKwon, TKMin, DSAhn, BHLee, YHSuh, JWKim, JWIwashita, SOmori, AIchinose, SNumata, OSeo, Jeong KonOh, YSSuh, Pann-Ghill
Keywords
PHOSPHATIDYLINOSITOL 4-KINASE; TYROSINE KINASE; SIGNALING MOLECULES; FACTOR 1-ALPHA; COMMON FOLD; C ISOZYMES; PH DOMAINS; MEMBRANE; BINDING; CELLS
Issue Date
200205
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.277, no.22, pp.19697 - 19702
Abstract
The pleckstrin homology (PH) domain is a small motif for membrane targeting in the signaling molecules. Phospholipase C (PLC)-γ1 has two putative PH domains, an NH2-terminal and a split PH domain. Here we report studies on the interaction of the PH domain of PLC-γ1 with translational elongation factor (EF)-1α, which has been shown to be a phosphatidylinositol 4-kinase activator. By pull-down of cell extract with the glutathione S-transferase (GST) fusion proteins with various domains of PLC-γ1 followed by peptide sequence analysis, we identified EF-1α as a binding partner of a split PH domain of PLC-γ1. Analysis by site-directed mutagenesis of the PH domain revealed that the β2-sheet of a split PH domain is critical for the interaction with EF-1α. Moreover, Dot-blot assay shows that a split PH domain specifically binds to phosphoinositides including phosphatidylinositol 4-phosphate and phosphatidylinositol 4, 5-bisphosphate (PIP2). So the PH domain of PLC-γ1 binds to both EF-1α and PlP2. The binding affinity of EF-1α to the GST·PH domain fusion protein increased in the presence of PIP2, although PIP2 does not bind to EF-1α directly. This suggests that EF-1α may control the binding affinity between the PH domain and PIP2. PLC-γ1 is substantially activated in the presence of EF-1α with a bell-shaped curve in relation to the molar ratio between them, whereas a double point mutant PLC-γ1 (Y509A/F510A) that lost its binding affinity to EF-1α shows basal level activity. Taken together, our data show that EF-1α plays a direct role in phosphoinositide metabolism of cellular signaling by regulating PLC-γ1 activity via a split PH domain.
URI
Go to Link
DOI
http://dx.doi.org/10.1074/jbc.M111206200
ISSN
0021-9258
Appears in Collections:
SLS_Journal Papers

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qr_code

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU