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Left–right asymmetry is initiated during chick embryogenesis in small domains near Hensen's node. Subsequently, broad asymmetric gene expression domains are established in the lateral plate mesoderm, ultimately determining the directionality of morphogenetic events. The transfer of asymmetric information from the node to the lateral plate is mediated by Caronte (Car), a novel member of the Cerberus/Dan...
SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling. During embryonic development, SOCS3 is highly expressed in erythroid lineage cells and is Epo independent. Transgene-mediated expression blocks fetal erythropoiesis, resulting in embryonic lethality. SOCS3 deletion results in an...
SOCS1 is an SH2-containing protein that is primarily expressed in thymocytes in a cytokine- and T cell receptor–independent manner. SOCS1 deletion causes perinatal lethality with death by 2–3 weeks. During this period thymic changes include a loss of cellularity and a switch from predominantly CD4+CD8+ to single positive cells. Peripheral T cells express activation antigens and proliferate to IL-2...
The crystal structure of FGF2 bound to a naturally occurring variant of FGF receptor 1 (FGFR1) consisting of immunoglobulin-like domains 2 (D2) and 3 (D3) has been determined at 2.8 Å resolution. Two FGF2:FGFR1 complexes form a 2-fold symmetric dimer. Within each complex, FGF2 interacts extensively with D2 and D3 as well as with the linker between the two domains. The dimer is stabilized by interactions...
WT1 encodes a zinc finger transcription factor implicated in kidney differentiation and tumorigenesis. In reporter assays, WT1 represses transcription from GC- and TC-rich promoters, but its physiological targets remain uncertain. We used hybridization to high-density oligonucleotide arrays to search for native genes whose expression is altered following inducible expression of WT1. The major target...
Measles virus (MV) infects 40 million persons and kills one million per year primarily by suppressing the immune system and afflicting the central nervous system (CNS). The lack of a suitable small animal model has impeded progress of understanding how MV causes disease and the development of novel therapies and improved vaccines. We tested a transgenic mouse line in which expression of the MV receptor...
We identified a seven-pass transmembrane receptor of the cadherin superfamily, designated Flamingo (Fmi), localized at cell–cell boundaries in the Drosophila wing. In the absence of Fmi, planar polarity was distorted. Before morphological polarization of wing cells along the proximal-distal (P-D) axis, Fmi was redistributed predominantly to proximal and distal cell edges. This biased localization...
Mice lacking suppressor of cytokine signaling-1 (SOCS1) develop a complex fatal neonatal disease. In this study, SOCS1−/− mice were shown to exhibit excessive responses typical of those induced by interferon γ (IFNγ), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNγ-dependent capacity to kill L. major parasites. The complex disease in SOCS1−/− mice was prevented...
A variety of proteins, including glycosylasparaginase, have recently been found to activate functions by self-catalyzed peptide bond rearrangements from single-chain precursors. Here we present the 1.9 Å crystal structures of glycosylasparaginase precursors that are able to autoproteolyze via an N → O acyl shift. Several conserved residues are aligned around the scissile peptide bond that is in a...
Nuclear receptors have been postulated to regulate gene expression via their association with histone acetylase (HAT) or deacetylase complexes. We report that hormone induces dramatic hyperacetylation at endogenous target genes through the HAT activity of p300/CBP. Unexpectedly, this hyperacetylation is transient and coincides with attenuation of hormone-induced gene activation. In exploring the underlying...
The organizer is a unique region in the gastrulating embryo that induces and patterns the body axis. It arises before gastrulation under the influence of the Nieuwkoop center. We show that during gastrulation, cell movements bring cells into and out of the chick organizer, Hensen's node. During these movements, cells acquire and lose organizer properties according to their position. A “node inducing...
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