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PDBsum entry 1fgy
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Signaling protein
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PDB id
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1fgy
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Grp1 ph domain with ins(1,3,4,5)p4
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Structure:
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Grp1. Chain: a. Fragment: pleckstrin homology domain (residues 261 - 387). Synonym: arf1 guanine nucleotide exchange factor and integrin binding protein homolog. Engineered: yes
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Source:
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Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.50Å
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R-factor:
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0.213
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R-free:
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0.247
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Authors:
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S.E.Lietzke,S.Bose,T.Cronin,J.Klarlund,A.Chawla,M.P.Czech, D.G.Lambright
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Key ref:
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S.E.Lietzke
et al.
(2000).
Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains.
Mol Cell,
6,
385-394.
PubMed id:
DOI:
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Date:
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29-Jul-00
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Release date:
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23-Aug-00
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PROCHECK
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Headers
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References
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O08967
(CYH3_MOUSE) -
Cytohesin-3 from Mus musculus
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Seq:
Struc:
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399 a.a.
127 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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DOI no:
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Mol Cell
6:385-394
(2000)
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PubMed id:
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Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains.
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S.E.Lietzke,
S.Bose,
T.Cronin,
J.Klarlund,
A.Chawla,
M.P.Czech,
D.G.Lambright.
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ABSTRACT
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Lipid second messengers generated by phosphoinositide (PI) 3-kinases regulate
diverse cellular functions through interaction with pleckstrin homology (PH)
domains in modular signaling proteins. The PH domain of Grp1, a PI
3-kinase-activated exchange factor for Arf GTPases, selectively binds
phosphatidylinositol 3,4,5-trisphosphate with high affinity. We have determined
the structure of the Grp1 PH domain in the unliganded form and bound to inositol
1,3,4,5-tetraphosphate. A novel mode of phosphoinositide recognition involving a
20-residue insertion within the beta6/beta7 loop explains the unusually high
specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding
typical of several PH domains including that of protein kinase B. When compared
to other PH domains, general determinants of 3-phosphoinositide recognition and
specificity can be deduced.
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Selected figure(s)
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Figure 5.
Figure 5. Localized Structural Changes Accompanying Head
Group BindingOverlay of the unliganded (magenta) and
Ins(1,3,4,5)P[4]-bound (cyan) forms of the Grp1 PH domain
following superposition of Cα atoms.
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Figure 6.
Figure 6. Comparison of Ins(1,3,4,5)P[4] Recognition by the
Grp1 and Btk PH Domains(A) Space-filling representation with
invariant residues of the signature motif shown in white and
nonconserved residues from the three SDRs highlighted in green
(β1/β2 loop), magenta (β3/β4 loop), and orange (hairpin
insertion).(B) Schematic diagram showing direct interactions
with the head group. Residues in the signature motif are
indicated in blue.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2000,
6,
385-394)
copyright 2000.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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N.A.Gokhale,
A.Zaremba,
and
S.B.Shears
(2011).
Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain.
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Biochem J,
434,
415-426.
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S.G.Jackson,
S.Al-Saigh,
C.Schultz,
and
M.S.Junop
(2011).
Inositol pentakisphosphate isomers bind PH domains with varying specificity and inhibit phosphoinositide interactions.
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BMC Struct Biol,
11,
11.
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B.Miao,
I.Skidan,
J.Yang,
A.Lugovskoy,
M.Reibarkh,
K.Long,
T.Brazell,
K.A.Durugkar,
J.Maki,
C.V.Ramana,
B.Schaffhausen,
G.Wagner,
V.Torchilin,
J.Yuan,
and
A.Degterev
(2010).
Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains.
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Proc Natl Acad Sci U S A,
107,
20126-20131.
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E.Kim
(2010).
Insulin resistance at the crossroads of metabolic syndrome: systemic analysis using microarrays.
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Biotechnol J,
5,
919-929.
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T.G.Kutateladze
(2010).
Translation of the phosphoinositide code by PI effectors.
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Nat Chem Biol,
6,
507-513.
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D.F.Ceccarelli,
and
F.Sicheri
(2009).
Grb-ing hold of insulin signaling.
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Nat Struct Mol Biol,
16,
803-804.
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F.Campa,
H.Y.Yoon,
V.L.Ha,
Z.Szentpetery,
T.Balla,
and
P.A.Randazzo
(2009).
A PH domain in the Arf GTPase-activating protein (GAP) ARAP1 binds phosphatidylinositol 3,4,5-trisphosphate and regulates Arf GAP activity independently of recruitment to the plasma membranes.
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J Biol Chem,
284,
28069-28083.
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I.Rodríguez-Escudero,
A.Andrés-Pons,
R.Pulido,
M.Molina,
and
V.J.Cid
(2009).
Phosphatidylinositol 3-Kinase-dependent Activation of Mammalian Protein Kinase B/Akt in Saccharomyces cerevisiae, an in Vivo Model for the Functional Study of Akt Mutations.
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J Biol Chem,
284,
13373-13383.
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J.D.Knight,
and
J.J.Falke
(2009).
Single-molecule fluorescence studies of a PH domain: new insights into the membrane docking reaction.
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Biophys J,
96,
566-582.
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R.S.Depetris,
J.Wu,
and
S.R.Hubbard
(2009).
Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14.
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Nat Struct Mol Biol,
16,
833-839.
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PDB code:
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S.V.Madhunapantula,
and
G.P.Robertson
(2009).
The PTEN-AKT3 signaling cascade as a therapeutic target in melanoma.
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Pigment Cell Melanoma Res,
22,
400-419.
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V.Laketa,
S.Zarbakhsh,
E.Morbier,
D.Subramanian,
C.Dinkel,
J.Brumbaugh,
P.Zimmermann,
R.Pepperkok,
and
C.Schultz
(2009).
Membrane-permeant phosphoinositide derivatives as modulators of growth factor signaling and neurite outgrowth.
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Chem Biol,
16,
1190-1196.
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B.E.Steinberg,
and
S.Grinstein
(2008).
Pathogen destruction versus intracellular survival: the role of lipids as phagosomal fate determinants.
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J Clin Invest,
118,
2002-2011.
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E.Macia,
M.Partisani,
C.Favard,
E.Mortier,
P.Zimmermann,
M.F.Carlier,
P.Gounon,
F.Luton,
and
M.Franco
(2008).
The pleckstrin homology domain of the Arf6-specific exchange factor EFA6 localizes to the plasma membrane by interacting with phosphatidylinositol 4,5-bisphosphate and F-actin.
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J Biol Chem,
283,
19836-19844.
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J.He,
R.M.Haney,
M.Vora,
V.V.Verkhusha,
R.V.Stahelin,
and
T.G.Kutateladze
(2008).
Molecular mechanism of membrane targeting by the GRP1 PH domain.
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J Lipid Res,
49,
1807-1815.
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K.D.Swanson,
Y.Tang,
D.F.Ceccarelli,
F.Poy,
J.P.Sliwa,
B.G.Neel,
and
M.J.Eck
(2008).
The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch.
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Mol Cell,
32,
564-575.
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PDB codes:
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K.E.Landgraf,
C.Pilling,
and
J.J.Falke
(2008).
Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH domain.
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Biochemistry,
47,
12260-12269.
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K.Hong,
L.Lou,
S.Gupta,
F.Ribeiro-Neto,
and
D.L.Altschuler
(2008).
A Novel Epac-Rap-PP2A Signaling Module Controls cAMP-dependent Akt Regulation.
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J Biol Chem,
283,
23129-23138.
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W.S.Park,
W.D.Heo,
J.H.Whalen,
N.A.O'Rourke,
H.M.Bryan,
T.Meyer,
and
M.N.Teruel
(2008).
Comprehensive identification of PIP3-regulated PH domains from C. elegans to H. sapiens by model prediction and live imaging.
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Mol Cell,
30,
381-392.
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Y.Yu,
and
J.C.Alwine
(2008).
Interaction between simian virus 40 large T antigen and insulin receptor substrate 1 is disrupted by the K1 mutation, resulting in the loss of large T antigen-mediated phosphorylation of Akt.
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J Virol,
82,
4521-4526.
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A.Rosenhouse-Dantsker,
and
D.E.Logothetis
(2007).
Molecular characteristics of phosphoinositide binding.
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Pflugers Arch,
455,
45-53.
|
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C.Frantz,
A.Karydis,
P.Nalbant,
K.M.Hahn,
and
D.L.Barber
(2007).
Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells.
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J Cell Biol,
179,
403-410.
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D.F.Ceccarelli,
I.M.Blasutig,
M.Goudreault,
Z.Li,
J.Ruston,
T.Pawson,
and
F.Sicheri
(2007).
Non-canonical interaction of phosphoinositides with pleckstrin homology domains of Tiam1 and ArhGAP9.
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J Biol Chem,
282,
13864-13874.
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PDB codes:
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D.Manna,
A.Albanese,
W.S.Park,
and
W.Cho
(2007).
Mechanistic basis of differential cellular responses of phosphatidylinositol 3,4-bisphosphate- and phosphatidylinositol 3,4,5-trisphosphate-binding pleckstrin homology domains.
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J Biol Chem,
282,
32093-32105.
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E.E.Kooijman,
D.P.Tieleman,
C.Testerink,
T.Munnik,
D.T.Rijkers,
K.N.Burger,
and
B.de Kruijff
(2007).
An electrostatic/hydrogen bond switch as the basis for the specific interaction of phosphatidic acid with proteins.
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J Biol Chem,
282,
11356-11364.
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J.P.DiNitto,
A.Delprato,
M.T.Gabe Lee,
T.C.Cronin,
S.Huang,
A.Guilherme,
M.P.Czech,
and
D.G.Lambright
(2007).
Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors.
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Mol Cell,
28,
569-583.
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PDB codes:
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Y.Jia,
K.K.Subramanian,
C.Erneux,
V.Pouillon,
H.Hattori,
H.Jo,
J.You,
D.Zhu,
S.Schurmans,
and
H.R.Luo
(2007).
Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5- trisphosphate signaling in neutrophils.
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Immunity,
27,
453-467.
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B.Fuss,
T.Becker,
I.Zinke,
and
M.Hoch
(2006).
The cytohesin Steppke is essential for insulin signalling in Drosophila.
|
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Nature,
444,
945-948.
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F.J.Tamarkin,
W.S.Kang,
J.J.Cohen,
M.A.Wheeler,
and
R.M.Weiss
(2006).
A role for Akt in the rapid regulation of inflammatory and apoptotic pathways in mouse bladder.
|
| |
Naunyn Schmiedebergs Arch Pharmacol,
373,
349-359.
|
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H.Teo,
D.J.Gill,
J.Sun,
O.Perisic,
D.B.Veprintsev,
Y.Vallis,
S.D.Emr,
and
R.L.Williams
(2006).
ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes.
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Cell,
125,
99.
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PDB codes:
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J.H.Hurley
(2006).
Membrane binding domains.
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Biochim Biophys Acta,
1761,
805-811.
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W.Wen,
J.Yan,
and
M.Zhang
(2006).
Structural characterization of the split pleckstrin homology domain in phospholipase C-gamma1 and its interaction with TRPC3.
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J Biol Chem,
281,
12060-12068.
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PDB code:
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C.Edlich,
G.Stier,
B.Simon,
M.Sattler,
and
C.Muhle-Goll
(2005).
Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin.
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Structure,
13,
277-286.
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PDB code:
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G.P.Robertson
(2005).
Functional and therapeutic significance of Akt deregulation in malignant melanoma.
|
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Cancer Metastasis Rev,
24,
273-285.
|
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G.Song,
G.Ouyang,
and
S.Bao
(2005).
The activation of Akt/PKB signaling pathway and cell survival.
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J Cell Mol Med,
9,
59-71.
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J.G.Carlton,
and
P.J.Cullen
(2005).
Coincidence detection in phosphoinositide signaling.
|
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Trends Cell Biol,
15,
540-547.
|
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J.Yan,
W.Wen,
W.Xu,
J.F.Long,
M.E.Adams,
S.C.Froehner,
and
M.Zhang
(2005).
Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of alpha-syntrophin.
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EMBO J,
24,
3985-3995.
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PDB codes:
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D.Komander,
A.Fairservice,
M.Deak,
G.S.Kular,
A.R.Prescott,
C.Peter Downes,
S.T.Safrany,
D.R.Alessi,
and
D.M.van Aalten
(2004).
Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates.
|
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EMBO J,
23,
3918-3928.
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PDB codes:
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K.R.Skowronek,
F.Guo,
Y.Zheng,
and
N.Nassar
(2004).
The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids.
|
| |
J Biol Chem,
279,
37895-37907.
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PDB code:
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P.Mitra,
Y.Zhang,
L.E.Rameh,
M.P.Ivshina,
D.McCollum,
J.J.Nunnari,
G.M.Hendricks,
M.L.Kerr,
S.J.Field,
L.C.Cantley,
and
A.H.Ross
(2004).
A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast.
|
| |
J Cell Biol,
166,
205-211.
|
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T.C.Cronin,
J.P.DiNitto,
M.P.Czech,
and
D.G.Lambright
(2004).
Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains.
|
| |
EMBO J,
23,
3711-3720.
|
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PDB codes:
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U.Roth,
K.Curth,
T.G.Unterman,
and
T.Kietzmann
(2004).
The transcription factors HIF-1 and HNF-4 and the coactivator p300 are involved in insulin-regulated glucokinase gene expression via the phosphatidylinositol 3-kinase/protein kinase B pathway.
|
| |
J Biol Chem,
279,
2623-2631.
|
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A.H.Kim,
T.Sasaki,
and
M.V.Chao
(2003).
JNK-interacting protein 1 promotes Akt1 activation.
|
| |
J Biol Chem,
278,
29830-29836.
|
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|
|
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|
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C.Brock,
M.Schaefer,
H.P.Reusch,
C.Czupalla,
M.Michalke,
K.Spicher,
G.Schultz,
and
B.Nürnberg
(2003).
Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101 phosphoinositide 3-kinase gamma.
|
| |
J Cell Biol,
160,
89-99.
|
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G.E.Cozier,
D.Bouyoucef,
and
P.J.Cullen
(2003).
Engineering the phosphoinositide-binding profile of a class I pleckstrin homology domain.
|
| |
J Biol Chem,
278,
39489-39496.
|
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M.A.Lemmon
(2003).
Phosphoinositide recognition domains.
|
| |
Traffic,
4,
201-213.
|
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M.Yun,
L.Keshvara,
C.G.Park,
Y.M.Zhang,
J.B.Dickerson,
J.Zheng,
C.O.Rock,
T.Curran,
and
H.W.Park
(2003).
Crystal structures of the Dab homology domains of mouse disabled 1 and 2.
|
| |
J Biol Chem,
278,
36572-36581.
|
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PDB codes:
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S.M.Singh,
and
D.Murray
(2003).
Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains.
|
| |
Protein Sci,
12,
1934-1953.
|
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V.L.Tybulewicz,
L.Ardouin,
A.Prisco,
and
L.F.Reynolds
(2003).
Vav1: a key signal transducer downstream of the TCR.
|
| |
Immunol Rev,
192,
42-52.
|
|
|
|
|
|
|
D.A.Prober,
and
B.A.Edgar
(2002).
Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing.
|
| |
Genes Dev,
16,
2286-2299.
|
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|
|
H.Nagaya,
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The most recent references are shown first.
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from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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