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PDBsum entry 1l6o
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Gene regulation
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PDB id
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1l6o
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Dapper, A dishevelled-Associated antagonist of beta-Catenin and jnk signaling, Is required for notochord formation.
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Authors
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B.N.Cheyette,
J.S.Waxman,
J.R.Miller,
K.Takemaru,
L.C.Sheldahl,
N.Khlebtsova,
E.P.Fox,
T.Earnest,
R.T.Moon.
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Ref.
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Dev Cell, 2002,
2,
449-461.
[DOI no: ]
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PubMed id
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Abstract
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Dapper was isolated in a screen for proteins interacting with Dishevelled, a key
factor in Wnt signaling. Dapper and Dishevelled colocalize intracellularly and
form a complex with Axin, GSK-3, CKI, and beta-catenin. Overexpression of Dapper
increases Axin and GSK-3 in this complex, resulting in decreased soluble
beta-catenin and decreased activation of beta-catenin-responsive genes. Dapper
also inhibits activation by Dishevelled of c-Jun N-terminal kinase (JNK), a
component of beta-catenin-independent Frizzled signaling. Inhibition of Dapper
activates both beta-catenin-responsive genes and an AP1-responsive promoter,
demonstrating that Dapper is a general Dishevelled antagonist. Depletion of
maternal Dapper RNA from Xenopus embryos results in loss of notochord and head
structures, demonstrating that Dapper is required for normal vertebrate
development.
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Figure 1.
Figure 1. Sequence(A) Schemata of Xenopus Dsh (XDsh) and
Dpr (XDpr) showing conserved domains DIX, PDZ, and DEP, and
leucine zipper (LZ) and PDZ binding (PDZ-B) domains,
respectively. Gray in XDsh indicates yeast two-hybrid bait.
Vertical arrows indicate the positions of XDsh mutations
discussed in the text. The horizontal arrow indicates the 5′
extent of XDpr clone obtained from the screen.(B) Alignment of
XDpr (X) with orthologs from mouse (M) and human (H). Black
residues are identical; gray residues are conserved; horizontal
arrow as in (A).
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Figure 7.
Figure 7. Dpr Expression(A–G) mRNA whole-mount in situ
hybridizations.(A) Sense controls: gastrula (bottom) and tailbud
(top).(B) Early gastrula (stage 10 vegetal view; top, dorsal;
dl, dorsal lip).(C) Early neurula (stage 14 dorsal view; top,
anterior; ant ne, anterior neurectoderm).(D) Early tailbud
(stage 19 dorsal view; top, anterior).(E and F) Tailbud (stage
21; [E], anterior view; [F], lateral view; arrows, neural folds;
ey, eye fields; tb, tailbud).(G) Tadpole (stage 41 lateral view;
left, anterior).(H) Northern analysis adult MDpr1 expression:
br, brain; hrt, heart; kd, kidney; lvr, liver; lng, lung; ml,
muscle; skn, skin; si, small intestine; spn, spleen; stm,
stomach; ts, testis; thy, thymus.
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The above figures are
reprinted
by permission from Cell Press:
Dev Cell
(2002,
2,
449-461)
copyright 2002.
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