T Curran

..These findings demonstrate that ApoER2 and VLDLR are essential for Reelin signaling and that no other receptor molecules can compensate for their role in mediating tyrosine phosphorylation of Dab1...

..Reelin appears to function as an instructive signal in the regulation of cell patterning during development...

..These results imply that, in addition to its essential role during neuronal migration, the Reelin pathway contributes to the formation of neuronal circuits in the central nervous system...

..This suggests that Dab1 accumulates in the absence of a Reln-evoked signal. Taken together, these results indicate that Dab1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain...

..These findings imply that the scrambler gene product may function in a molecular pathway critical for neuronal migration that is tightly linked to, but downstream of, reelin...

..In dissociated neurons, apoE reduces the level of Reelin-induced tyrosine phosphorylation of Dab1. These data suggest that Reelin directs neuronal migration by binding to VLDLR and ApoER2...

..Dab1 and APLP1 are expressed in similar cell populations in developing and adult brain tissue. These results suggest that Dab1 may function, at least in part, through association with APLP1 in the brain...

..Here we report that, although Src can phosphorylate all five tyrosines in vitro, Tyr(198) and Tyr(220) represent the major sites of Reelin-induced Dab1 phosphorylation in embryonic neurons...

..Our results indicate that mPcdh18 participates in signaling pathways involving PTB-containing proteins and suggest that it may play a role during brain development...

..Ptc+/- p53-/- mice provide a useful model for investigation of the molecular bases of medulloblastoma and for evaluation of the efficacy of therapeutic intervention strategies in a spontaneously arising endogenous brain tumor...

..The reelin gene product seems to function as an instructive signal in the regulation of neuronal migration...

..Recent studies have also suggested a role for the Reelin pathway in axonal branching, synaptogenesis, and pathology underlying neurodegeneration...

..The similar phenotypes of reeler, scrambler, yotari and mdab1 null mice indicate that Reelin and mDab1 function as signalling molecules that regulate cell positioning in the developing brain...

..This raises the possibility that the Reelin/Dab1 signaling pathway contributes to formation of intraretinal circuitry in the neural retina...

..Furthermore, the recent identification of genes that may function in the Reelin signaling pathway advances our knowledge of the molecular basis of neuronal migration...

..Finally, the Smoothened inhibitor, hedgehog antagonist, did not block growth of tumors arising from Sufu inactivation. These data demonstrate that Sufu is essential for development and functions as a tumor suppressor...

..These data indicate that haploinsufficiency of ptc is sufficient to promote oncogenesis in the central nervous system...

..They have been implicated in the Reelin pathway in cortical development. But new genetic studies have revealed that, while beta(1) integrin plays a role in formation of the basement membrane, it is not essential for neuronal migration...

..The assay also permits discrimination of heterozygous from wild-type mice. These findings provide a strategy for the characterization of the early anatomical and physiological consequences of the reeler mutation...

..Inhibition of histone deacetylase, which associates with methylated DNA, also caused reversion. These results suggest that fos may transform cells through alterations in DNA methylation and in histone deacetylation...

..They also suggest that Reelin promotes maturation of single fibers and synaptogenesis by entorhinal afferents...

..Together, these studies provide the sequence information and genetic tools for performing more detailed analyses of RELN in an attempt to define its role in human brain development and possibly in human disease...

..Our data suggest that the effects of thyroid hormone on neuronal migration may be in part mediated through the control of reelin and dab1 expression during brain ontogenesis...

..The encoded protein resembles extracellular matrix proteins involved in cell adhesion. The reeler phenotype thus seems to reflect a failure of early events associated with brain lamination which are normally controlled by reelin...

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..Thus, unlike the two rl alleles described previously, rltg provides a molecular probe that can now be used to identify and isolate the rl gene...

..This complex pattern of cellular and regional expression is consistent with Reelin having multiple roles in brain development and adult brain function...

..A single-size (3.4 kilobases long) class of RNA hybridizing to the viral fos probe was identified in FBJ-MSV-transformed cells...

..The AGS phenotype identifies a novel neurological role for TR beta...

..This suggests that, contrary to in vitro models, RXRs may be dispensable and that TRbeta may function in vivo by an RXR-independent mechanism in the auditory system and pituitary-thyroid axis...

..Our results identify Tr beta as an essential transcription factor for auditory development and indicate that distinct Tr genes serve certain unique functions...

..This information was used to visualize the consequences of DNA bending by Fos and Jun for the structures of Fos-Jun-DNA and Jun-DNA complexes...

..Moreover, UV-crosslinking studies demonstrated that Fos and Jun contact DNA directly and that both proteins interacted equivalently with either strand of the AP-1-binding site...

..Thus, Egr-1 and c-fos are often coregulated with strikingly similar kinetics. These results, in conjunction with the Egr-1 primary structure, suggest that Egr-1 may function as a transcriptional regulator in diverse biological processes...

..It undergoes extensive post-translational modification in the lysate, particularly in the presence of additional cAMP. The c-fos protein synthesized in vitro appears to be phosphorylated by the cAMP-dependent protein kinase...

..5, and 0.5 kb were separated by four regions of nonhomology of 0.76, 0.55, 0.1, and 0.1 kb from 5' to 3' with respect to the FBJ-MSV genome. The size of these sequences showed striking similarity in both c-fos(mouse) and c-fos(human)...

..Immunofluorescence data indicate that the level of p55c-fos in normal mouse amnion cells is similar to that found in fibroblasts transformed by the v-fos or c-fos proteins...

..Our studies show that normal cellular protein can induce transformation when expressed in an inappropriate cell type...

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..This study suggests a novel link between transcription factor regulation, oxidative signalling and DNA repair processes in higher eukaryotes...

..Although the NMDA receptor has been implicated in several aspects of neurodevelopment, overall neuroanatomy of NR1-/- mice appeared normal. Pathological evidence suggested that respiratory failure was the ultimate cause of death...

..These results indicate that Maf and Nrl together with Fos and Jun family proteins form a bZIP protein superfamily whose members can form an array of heterodimers that have overlapping DNA binding specificities...

..Our results suggest that cell transformation by Fos requires increased expression of a target gene(s) with a long-lived product(s) that must reach a critical level...

..The molecular cloning of NFATp should allow detailed analysis of a T cell transcription factor that is central to initiation of the immune response...

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..These results suggest that dimerization induces a conformational alteration in the basic region of Fos and Jun that promotes an association with TFIIE-34 and TFIIF, thus contributing to transcription initiation...

..Importantly, we have also determined that Ref-1 can stimulate p53 transactivation in vivo. This is the first example of a noncovalent protein modifier of p53 function identified in cells...

..However, although TR alpha alone can mediate thyroid hormone induced TSH suppression, TR beta enhances the sensitivity of TSH down-regulation and may be essential for the complete suppression of TSH...

..The observed consensus sequence was Pro-Leu-Ser/Thr-Pro. We propose that this sequence forms part of a substrate structure that is recognized by the ERT protein kinase...