Structural Characterization of the Interaction between a Pleckstrin Homology Domain and Phosphatidylinositol 4,5-Bisphosphate

Biochemistry ◽  
1995 ◽  
Vol 34 (31) ◽  
pp. 9859-9864 ◽  
Author(s):  
John E. Harlan ◽  
Ho Sup Yoon ◽  
Philip J. Hajduk ◽  
Stephen W. Fesik
Keyword(s):  
Structural Characterization ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology

Expression and characterization of a pleckstrin homology domain in phospholipase C, PLC-η1

2007 ◽  
Vol 56 (2) ◽  
pp. 247-252 ◽  
Author(s):  
Toru Imai ◽  
Kouki Kasai ◽  
Junichi Kurita ◽  
Kiyoko Fukami ◽  
Mitsuru Tashiro ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology

scholarly journals Characterization of RhoA-binding Kinase ROKα Implication of the Pleckstrin Homology Domain in ROKα Function Using Region-specific Antibodies

2002 ◽  
Vol 277 (15) ◽  
pp. 12680-12688 ◽  
Author(s):  
Xiang-qun Chen ◽  
Ivan Tan ◽  
Chong Han Ng ◽  
Christine Hall ◽  
Louis Lim ◽  
...  
Keyword(s):  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Specific Antibodies

Functional characterization of the pleckstrin homology domain of a cellulose synthase from the oomycete Saprolegnia monoica

2012 ◽  
Vol 417 (4) ◽  
pp. 1248-1253 ◽  
Author(s):  
Johanna Fugelstad ◽  
Christian Brown ◽  
Elvira Hukasova ◽  
Gustav Sundqvist ◽  
Arne Lindqvist ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Cellulose Synthase ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology

scholarly journals Characterization of Pak2p, a Pleckstrin Homology Domain-containing, p21-activated Protein Kinase from Fission Yeast

1998 ◽  
Vol 273 (29) ◽  
pp. 18490-18498 ◽  
Author(s):  
Mary Ann Sells ◽  
Justin T. Barratt ◽  
Juliane Caviston ◽  
Sabine Ottilie ◽  
Ekkehard Leberer ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fission Yeast ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology

scholarly journals Structural and Functional Characterization of the Kindlin-1 Pleckstrin Homology Domain

2012 ◽  
Vol 287 (52) ◽  
pp. 43246-43261 ◽  
Author(s):  
Luke A. Yates ◽  
Craig N. Lumb ◽  
Nina N. Brahme ◽  
Ruta Zalyte ◽  
Louise E. Bird ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology

scholarly journals Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors

2005 ◽  
Vol 385 (2) ◽  
pp. 399-408 ◽  
Author(s):  
Stanley F. BARNETT ◽  
Deborah DEFEO-JONES ◽  
Sheng FU ◽  
Paula J. HANCOCK ◽  
Kathleen M. HASKELL ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Pleckstrin Homology Domain ◽  
Ph Domain ◽  
Pleckstrin Homology ◽  
Time Resolved ◽  
Akt Isoforms ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
A Site

We developed a high-throughput HTRF (homogeneous time-resolved fluorescence) assay for Akt kinase activity and screened approx. 270000 compounds for their ability to inhibit the three isoforms of Akt. Two Akt inhibitors were identified that exhibited isoenzyme specificity. The first compound (Akt-I-1) inhibited only Akt1 (IC50 4.6 μM) while the second compound (Akt-I-1,2) inhibited both Akt1 and Akt2 with IC50 values of 2.7 and 21 μM respectively. Neither compound inhibited Akt3 nor mutants lacking the PH (pleckstrin homology) domain at concentrations up to 250 μM. These compounds were reversible inhibitors, and exhibited a linear mixed-type inhibition against ATP and peptide substrate. In addition to inhibiting kinase activity of individual Akt isoforms, both inhibitors blocked the phosphorylation and activation of the corresponding Akt isoforms by PDK1 (phosphoinositide-dependent kinase 1). A model is proposed in which these inhibitors bind to a site formed only in the presence of the PH domain. Binding of the inhibitor is postulated to promote the formation of an inactive conformation. In support of this model, antibodies to the Akt PH domain or hinge region blocked the inhibition of Akt by Akt-I-1 and Akt-I-1,2. These inhibitors were found to be cell-active and to block phosphorylation of Akt at Thr308 and Ser473, reduce the levels of active Akt in cells, block the phosphorylation of known Akt substrates and promote TRAIL (tumour-necrosis-factor-related apoptosis-inducing ligand)-induced apoptosis in LNCap prostate cancer cells.

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