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Biomedical subjects

F Veríssimo

Publications and source records attributed to F Veríssimo.

5 recordsLinked to original sources
PubMed2006

Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway.

The subfamily of WNK (with no K= lysine) protein kinases has four human members and germline mutations in the WNK1 and WNK4 genes were recently found to cause pseudohypoaldosteronism type II, a familial hypertension disease. Here, we describe cloning and functional analysis of a further WNK member, human WNK3. Endogenous WNK3 protein is an active protein kinase when immunoprecipitated from cells and its overexpression increases the survival of HeLa cells by delaying the onset of apoptosis. Suppression of endogenous WNK3 protein by RNA interference accelerates the apoptotic response and promotes the activation of caspase-3. The mechanism of WNK3 action involves interaction with procaspase-3 and heat-shock protein 70. These results demonstrate a role for WNK3 in promoting cell survival and suggest a mechanism at the level of procaspase-3 activation.

Apoptosis↗
PubMed2003

Construction and characterization of CD4-independent infectious recombinant HIV-2 molecular clones.

Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) differ in their pathogenic mechanisms as evidenced by lower rate of disease progression, lower transmission rates and lower viral load in peripheral blood for HIV-2. One of the many factors that are involved in these characteristics is the interaction between viral glycoproteins and cellular receptors. The study of these interactions in an HIV-2 model could lead to important conclusions regarding pathogenesis and transmission mechanisms of HIV-2 infection. Here we report the design of a method enabling the construction of recombinant proviral HIV-2 DNAs in a moderate copy number plasmid that allows the analysis of env gene structure and functionality. This method constitutes an important tool for the study of HIV-2 env glycoproteins and for the mappings of genetic determinants of HIV-2 coreceptor usage and CD4-independent interaction. Furthermore, this knowledge will help towards the understanding of the different pathogenic mechanisms of HIV-1 and HIV-2.

CD4 Antigens↗
PubMed2001

WNK kinases, a novel protein kinase subfamily in multi-cellular organisms.

We have cloned and characterized a novel human serine/threonine protein kinase gene from chromosome 12p13.3 encoding 2382 amino acids. Remarkably, the catalytic domain sequence contains a cysteine in place of a lysine residue conserved in subdomain II of most kinases. The same amino acid alteration was recently described for rat WNK1 (with no K=lysine) in which another nearby lysine residue was shown to confer kinase activity to the protein. Rat WNK1 is 85% identical to a splice variant lacking exons 11 and 12 of the described human kinase which we have called human WNK1. The WNK1 catalytic domain has closest homology with human PAK2, MEKK3, and Raf-1. Three additional, partial human protein kinase sequences, WNK2, WNK3 and WNK4, are also reported here with catalytic domains that are 95% homologous to WNK1. These genes differ both in chromosomal location and tissue-specific expression. Moreover, we have identified in the database a total of 18 WNK-related genes, all exclusively from multi-cellular organisms, which share a WNK kinase sequence signature within subdomains I and II of the catalytic domain. We suggest that they constitute a novel subfamily of protein kinases that evolved together with cell adhesion and tissue-formation.

Amino Acid Motifs↗
PubMed2000

Small GTPase Rac1: structure, localization, and expression of the human gene.

Rac1 is a member of the Rho family of small GTPases involved in signal transduction pathways that control proliferation, adhesion, and migration of cells during embryonic development and invasiveness of tumor cells. Here we present the complete structure of the human RAC1 gene and characterize its expression. The gene comprises 7 exons over a length of 29 kb and is localized to chromosome 7p22. The GC-rich gene promoter shows characteristics of a housekeeping gene and Northern blot studies revealed ubiquitous expression of two rac1 transcripts, 1.2 and 2.5 kb in size. The two transcripts are expressed in tissue-specific ratios, reflecting competition between two alternative polyadenylation sites. The RAC1 but not RAC2 gene contains an additional exon 3b that is included by alternative splicing into the variant Rac1b, a constitutively active mutant which induces the formation of lamellipodia in fibroblasts. These data indicate that the RAC1 gene encodes two signaling GTPases. The gene structure reported here will enable studies on the regulation of RAC1 expression during tumorigenesis and development.

5' Untranslated Regions↗