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Biomedical subjects

E Turco

Publications and source records attributed to E Turco.

At least 19 recordsLinked to original sources
PubMed2004

Integrin regulation of epidermal growth factor (EGF) receptor and of EGF-dependent responses.

Integrin signalling co-ordinates with signalling originating from growth factor receptors in the co-operative control of cell proliferation, survival and migration. Increasing evidence suggests that integrins form physical complexes at the cell membrane with growth factor receptors, giving rise to signalling platforms at the adhesive sites. It is probable that at these sites integrins regulate adhesion and at the same time physically constrain and direct the response to soluble growth factors towards proliferation or survival stimuli. These co-operative effects might depend on integrin ability to activate growth factor receptors. In the present paper, we summarize our recent study showing that integrin-dependent adhesion triggers ligand-independent EGFR (epidermal growth factor receptor) activation to transduce downstream signalling. In addition, we also show that integrin-induced signalling pathways are necessary for EGF-dependent transcriptional response, demonstrating the requirement of the co-operation between cell-matrix adhesion and EGFR to achieve full biological responses.

Animals↗
PubMed2000

Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis.

Citron-kinase (Citron-K) has been proposed by in vitro studies as a crucial effector of Rho in regulation of cytokinesis. To further investigate in vivo its biologic functions, we have inactivated Citron-K gene in mice by homologous recombination. Citron-K-/- mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with depletion of specific neuronal populations. These abnormalities arise during development of the central nervous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in specific neuronal precursors. Moreover, they suggest a novel molecular mechanism for a subset of human malformative syndromes of the CNS.

Animals↗
PubMed1998

Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron.

We have identified a novel serine/threonine kinase belonging to the myotonic dystrophy kinase family. The kinase can be produced in at least two different isoforms: a approximately 240-kDa protein (Citron Rho-interacting kinase, CRIK), in which the kinase domain is followed by the sequence of Citron, a previously identified Rho/Rac binding protein; a approximately 54-kDa protein (CRIK-short kinase (SK)), which consists mostly of the kinase domain. CRIK and CRIK-SK proteins are capable of phosphorylating exogenous substrates as well as of autophosphorylation, when tested by in vitro kinase assays after expression into COS7 cells. CRIK kinase activity is increased severalfold by coexpression of costitutively active Rho, while active Rac has more limited effects. Kinase activity of endogenous CRIK is indicated by in vitro kinase assays after immunoprecipitation with antibodies recognizing the Citron moiety of the protein. When expressed in keratinocytes, full-length CRIK, but not CRIK-SK, localizes into corpuscular cytoplasmic structures and elicits recruitment of actin into these structures. The previously reported Rho-associated kinases ROCK I and II are ubiquitously expressed. In contrast, CRIK exhibits a restricted pattern of expression, suggesting that this kinase may fulfill a more specialized function in specific cell types.

Amino Acid Sequence↗
PubMed1998

The biochemistry of gene therapy for AIDS.

Gene therapy has enormous potential and could in the near future involve the clinical biochemist in monitoring its efficacy. The involvement of clinical biochemists in this field could be not only in evaluating the impact of a gene-based strategy on disease progression, but also in measuring the expression of the products of therapeutic genes in treated individuals. Indeed, gene therapy presents new possibilities for the treatment of many diseases and, in particular, merits consideration in the treatment of a fatal disease like AIDS. The aim of this paper is to review the biochemical basis and clinical relevance of the gene therapy approaches directed towards the inhibition of human immunodeficiency virus type-1. We discuss the goals which have been achieved, the problems which have occurred and the efforts that are being made to solve them. In this regard, particular attention is paid to new strategies targeting 'therapeutic' enzymes to human immunodeficiency virus type-1 nucleic acids.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Coexpression of platelet-derived growth factor (PDGF) B chain and PDGF B-type receptor in human gliomas.

In this study we analyzed the expression of mRNA for PDGF-B and PDGF B-type receptor (PDGFrecB) in 42 biopsy specimens from human astrocytic gliomas and other brain tumors. All gliomas expressed PDGF-B mRNA at higher levels than found in peritumoral and normal nervous tissues. Levels of PDGF-B transcripts correlated strongly with those of mRNA for glial fibrillary acidic protein. Thus, the production of PDGF-B mRNA may be attributed mainly to tumoral glial cells. PDGFrecB transcripts were found in 24 out of 29 gliomas, in agreement with the hypothesis of an autocrine growth stimulation in these tumors. Moreover, mean levels of PDGFrecB expression were higher in glioblastomas than in astrocytomas and over 30-fold higher in meningiomas than in gliomas. This suggests that in gliomas PDGFrecB can be expressed also by vascular elements, in agreement with the hypothesized existence of a paracrine mechanism that may be responsible for the endothelial hyperplasias.

Astrocytoma↗
PubMed1990

The X boxes from promoters of HLA class II B genes at different loci do not complete for nuclear protein-specific binding.

Expression of HLA class II genes is coordinately regulated by cis-acting elements present in their promoter regions immediately upstream from the 5' end of their transcription start sites. Trans-acting factors from the nuclear proteins of the cell are able to positively or negatively regulate transcription of these genes by binding to highly conserved sequences, called boxes. After cloning the promoter regions of all the transcribed class II B genes present in the cell line Priess, we were able to identify certain protein-box complexes and to determine the affinity of these proteins for their respective boxes by comparing promoter boxes of each gene to those of the other genes. Different nuclear proteins seemed to bind to the X boxes of the different class II B genes tested. In the case of the Y box-protein complexes, the various Y boxes competed with similar affinities. The protein(s) which specifically bound to the DRB1-CCAAT box also bound to DPB1-CCAAT box, but completely failed to bind the homologous box from DQB1. Further, CCAAT box-specific protein(s) did not bind to the Y box of the same gene, excluding the possibility that these proteins just recognize the reverse CCAAT box (ATTGG) present within Y.

Amino Acid Sequence↗
PubMed1988

First domain encoding sequence mediates human class II beta-chain gene cross-hybridization.

HLA class II molecules are surface heterodimers which are essential in the initiation of immune responses. The amount of polymorphism expressed by the different class II molecules is largely dependent on the polymorphic structure of their beta chains. Cross-hybridization between class II beta genes frequently hampered restriction fragment length polymorphism analysis of donor genomic DNA. In this report we show that the cross-hybridization between human class II beta genes is mediated by a region of high homology, rich in C and G residues, between the first domain encoding sequences of DP, DQ, and DR genes. The removal of the DNA segment containing this region from the fragments used as labeled probes against the corresponding fragments of the genes at other loci or against endonuclease digested genomic DNA completely eliminated or drastically reduced the cross-hybridization. Also, the RFLP patterns generated with the shortened probes were more informative and much simpler to interpret than were these generated with probes made from the original genes.

Base Sequence↗
PubMed1988

The beta-chains of DP4 molecules from different haplotypes are encoded by the same gene.

The nucleotide sequence of a complete cDNA gene from a DP4-positive HLA-homozygous cell line, PGF, has been determined. This sequence is identical to the exon sequences in a genomic clone derived from another DP4-positive cell line, Priess. In contrast, our DP cDNA sequence shares only limited homology with partial cDNA sequences obtained from clones of three DP4-negative cell lines. On the basis of these results, we conclude that the phenotypic variation of DP alleles is directly attributable to the nucleotide sequence heterogeneity of DP-beta genes. That is, each phenotypic allelic form of DP antigen corresponds to a distinctly different DP-beta gene. Furthermore, this correspondence is found to be unaffected by the markers present at the DQ and DR loci, since the haplotypes of the PGF and Priess cell lines are, respectively, DR2,DQw1,DP4 and DR4,DQw3,DP4.

Amino Acid Sequence↗
PubMed1987

Allelic forms of the alpha- and beta-chain genes encoding DQw1-positive heterodimers.

On chromosome 6, in the HLA region, the DQ subregion is located immediately centromeric to the DR subregion. Even though only three serological specificities to date have been officially recognized (DQw1, DQw2, and DQw3), it seems likely that the phenotypical polymorphism expressed by DQ molecules is much more complex. There are reasons to believe that fixed alpha-beta combinations exist, each of them associated with a different DR allele. DQw1 is a determinant present on DQ molecules that are found associated with DR1-, DR2-, and DRw6-positive haplotypes. By restriction fragment length polymorphism analysis, we recognized three allelic DQ-alpha and three allelic DQ-beta patterns associated with DQw1. In addition, one of these alpha/beta pairs associated with DR1, two with DR2, and a fourth with DRw6. We have obtained evidence using nucleotide sequencing that there are as many allelic forms of DQ-alpha and DQ-beta genes as there are different molecular DQ-alpha and DQ-beta patterns. The DQ-alpha and DQ-beta chains of DQw1-positive molecules each are encoded by at least three distinctly different allelic genes, and particular alpha/beta gene combinations are associated with the same DR alleles as their corresponding molecular alpha/beta pairs.

Alleles↗
PubMed1981

Microdissection and cloning of DNA from a specific region of Drosophila melanogaster polytene chromosomes.

Fragments from section 3 of the salivary gland X chromosome of D. melanogaster were dissected with a micromanipulator. The DNA was extracted, cut and ligated to a lambda vector in a volume of a few nanoliters in an oil chamber monitored through a microscope. From about 10 pg of DNA we obtained 80 recombinant clones, a sample of which were analysed and shown to contain Drosophila DNA which hybridises in situ to the region of section 3 of the X chromosome. With this technique we can isolate clones from any desired region as small as 200 kb from the euchromatic arms of polytene chromosomes.

Bacteriophage lambda↗