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

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Pleckstrin homology domains of phospholipase C-gamma 1 directly interact with beta-tubulin for activation of phospholipase C-gamma 1 and reciprocal modulation of beta-tubulin function in microtubule assembly

Cited 28 times inthomson ciCited 27 times inthomson ci
Title
Pleckstrin homology domains of phospholipase C-gamma 1 directly interact with beta-tubulin for activation of phospholipase C-gamma 1 and reciprocal modulation of beta-tubulin function in microtubule assembly
Author
Chang, JSKim, SKKwon, TKBae, SSMin, DSLee, YHKim, SOSeo, Jeong KonChoi, Jang HyunSuh, Pann-Ghill
Keywords
PROTEIN-KINASE-C; NUCLEOTIDE EXCHANGE FACTOR; GROWTH-FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; POLYMERIZATION DYNAMICS; SIGNALING MOLECULES; ARACHIDONIC-ACID; ALPHA-SUBUNITS; GAMMA-SUBUNITS; PH DOMAINS
Issue Date
200502
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.280, no.8, pp.6897 - 6905
Abstract
Phosphoinositide-specific phospholipase C-γ1 (PLC-γ1) has two pleckstrin homology (PH) domains, an N-terminal domain and a split PH domain. Here we show that pull down of NIH3T3 cell extracts with PLC-γ1 PH domain-glutathione S-transferase fusion proteins, followed by matrix-assisted laser desorption ionization-time of flight-mass spectrometry, identified β-tubulin as a binding protein of both PLC-γ1 PH domains. Tubulin is a main component of microtubules and mitotic spindle fibers, which are composed of α- and β-tubulin heterodimers in all eukaryotic cells. PLC-γ1 and β-tubulin colocalized in the perinuclear region in COS-7 cells and cotranslocated to the plasma membrane upon agonist stimulation. Membrane-targeted translocation of depolymerized tubulin by agonist stimulation was also supported by immunoprecipitation analyses. The phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolyzing activity of PLC-γ1 was substantially increased in the presence of purified tubulin in vitro, whereas the activity was not promoted by bovine serum albumin, suggesting that β-tubulin activates PLC-γ1. Furthermore, indirect immunofluorescent microscopy showed that PLC-γ1 was highly concentrated in mitotic spindle fibers, suggesting that PLC-γ1 is involved in spindle fiber formation. The effect of PLC-γ1 in microtubule formation was assessed by overexpression and silencing PLC-γ1 in COS-7 cells, which resulted in altered microtubule dynamics in vivo. Cells overexpressing PLC-γ1 showed higher microtubule densities than controls, whereas PLC-γ1 silencing with small interfering RNAs led to decreased microtubule network densities as compared with control cells. Taken together, our results suggest that PLC-γ1 and β-tubulin transmodulate each other, i.e. that PLC-γ1 modulates microtubule assembly by β-tubulin, and β-tubulin promotes PLC-γ1 activity.
URI
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DOI
http://dx.doi.org/10.1074/jbc.M406350200
ISSN
0021-9258
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