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- Fuentealba LC, LC, et al.
(författare)
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Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal.
- 2007
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 131:5, s. 980-993
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Tidskriftsartikel (refereegranskat)abstract
- BMP receptors determine the intensity of BMP signals via Smad1 C-terminal phosphorylations. Here we show that a finely controlled cell biological pathway terminates this activity. The duration of the activated pSmad1Cter signal was regulated by sequential Smad1 linker region phosphorylations at conserved MAPK and GSK3 sites required for its polyubiquitinylation and transport to the centrosome. Proteasomal degradation of activated Smad1 and total polyubiquitinated proteins took place in the centrosome. Inhibitors of the Erk, p38, and JNK MAPKs, as well as GSK3 inhibitors, prolonged the duration of a pulse of BMP7. Wnt signaling decreased pSmad1GSK3 antigen levels and redistributed it from the centrosome to cytoplasmic LRP6 signalosomes. In Xenopus embryos, it was found that Wnts induce epidermis and that this required an active BMP-Smad pathway. Epistatic experiments suggested that the dorsoventral (BMP) and anteroposterior (Wnt/GSK3) patterning gradients are integrated at the level of Smad1 phosphorylations during embryonic pattern formation.
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| 3. |
- Pera, Edgar, et al.
(författare)
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Exploration of the extracellular space by a large-scale secretion screen in the early Xenopus embryo
- 2005
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Ingår i: International Journal of Developmental Biology. - : UPV/EHU Press. - 1696-3547 .- 0214-6282. ; 49:7, s. 781-796
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Tidskriftsartikel (refereegranskat)abstract
- Secreted proteins playa crucial role in intercellular communication during embryogenesis and in the adult. We recently described a novel method, designated as secretion cloning, that allows identifying extracellular proteins exclusively based on their ability to be secreted by transfected cells. In this paper, we present the results of a large-scale screening of more than 90,000 clones from three cDNA expression libraries constructed from early Xenopus embryos. Of 170 sequenced clones, 65 appeared to encode secreted proteins; 26 clones (40%) were identical to previously known Xenopus genes, 25 clones (38%) were homologous to other genes identified in various organisms and 14 clones (22%) were novel. Apart from these bona fide secreted proteins, we also isolated lysosomal or other secretory pathway proteins and some cytoplasmic proteins commonly found in body fluids. Among the novel secreted proteins were two putative growth factors of the Granulin family, termed xGra1 and xGra2; they are structurally similar to EGF and TGF alpha and show a spotted expression pattern in the epidermis. Another secreted protein, designated xSOUL, belongs to the family of heme-binding proteins and exhibits distinct expression in the early brain. Athird protein, termed Xystatin, is related to cysteine proteinase inhibitors. Our results indicate that secretion cloning is an effective and generally useful tool for the unbiased isolation of secreted proteins.
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