PMID- 10570958
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20190707
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 238
IP  - 2
DP  - 1999 Oct 1
TI  - Functional and structural diversity of the human Dickkopf gene family.
PG  - 301-13
AB  - Wnt proteins influence many aspects of embryonic development, and their activity 
      is regulated by several secreted antagonists, including the Xenopus Dickkopf-1
      (xDkk-1) protein. xDkk-1 inhibits Wnt activities in Xenopus embryos and may play 
      a role in induction of head structures. Here, we characterize a family of human
      Dkk-related genes composed of Dkk-1, Dkk-2, Dkk-3, and Dkk-4, together with a
      unique Dkk-3 related protein termed Soggy (Sgy). hDkks 1-4 contain two distinct
      cysteine-rich domains in which the positions of 10 cysteine residues are highly
      conserved between family members. Sgy is a novel secreted protein related to
      Dkk-3 but which lacks the cysteine-rich domains. Members of the Dkk-related
      family display unique patterns of mRNA expression in human and mouse tissues, and
      are secreted when expressed in 293T cells. Furthermore, secreted hDkk-2 and
      hDkk-4 undergo proteolytic processing which results in cleavage of the second
      cysteine-rich domain from the full-length protein. Members of the human
      Dkk-related family differ not only in their structures and expression patterns,
      but also in their abilities to inhibit Wnt signaling. hDkk-1 and hDkk-4, but not 
      hDkk-2, hDkk-3 or Sgy, suppress Wnt-induced secondary axis induction in Xenopus
      embryos. hDkk-1 and hDkk-4 do not block axis induction triggered either by
      Xenopus Dishevelled (Xdsh) or Xenopus Frizzled-8 (Xfz8), both of which function
      to transduce signals from Wnt ligands. Thus, hDkks 1 and 4 may inhibit Wnt
      activity by a mechanism upstream of Frizzled. Our findings highlight the
      structural and functional heterogeneity of human Dkk-related proteins.
FAU - Krupnik, V E
AU  - Krupnik VE
AD  - Department of Microbiology and Molecular Genetics, Harvard Medical School and
      Division of Molecular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 
      02215, USA.
FAU - Sharp, J D
AU  - Sharp JD
FAU - Jiang, C
AU  - Jiang C
FAU - Robison, K
AU  - Robison K
FAU - Chickering, T W
AU  - Chickering TW
FAU - Amaravadi, L
AU  - Amaravadi L
FAU - Brown, D E
AU  - Brown DE
FAU - Guyot, D
AU  - Guyot D
FAU - Mays, G
AU  - Mays G
FAU - Leiby, K
AU  - Leiby K
FAU - Chang, B
AU  - Chang B
FAU - Duong, T
AU  - Duong T
FAU - Goodearl, A D
AU  - Goodearl AD
FAU - Gearing, D P
AU  - Gearing DP
FAU - Sokol, S Y
AU  - Sokol SY
FAU - McCarthy, S A
AU  - McCarthy SA
LA  - eng
SI  - GENBANK/AF177394
SI  - GENBANK/AF177395
SI  - GENBANK/AF177396
SI  - GENBANK/AF177397
SI  - GENBANK/AF177398
SI  - GENBANK/AF177399
SI  - GENBANK/AF177400
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (DKK1 protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (Dkk1 protein, mouse)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Xenopus Proteins)
RN  - 0 (dkk1 protein, Xenopus)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers
MH  - Female
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Multigene Family
MH  - Protein Processing, Post-Translational
MH  - Proteins/*genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - Sequence Homology, Amino Acid
MH  - Xenopus/embryology
MH  - Xenopus Proteins
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - S0378111999003650 [pii]
AID - 10.1016/s0378-1119(99)00365-0 [doi]
PST - ppublish
SO  - Gene. 1999 Oct 1;238(2):301-13. doi: 10.1016/s0378-1119(99)00365-0.