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1.
Int J Mol Sci ; 24(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38139452

RESUMO

In the microenvironment, cell interactions are established between different cell types to regulate their migration, survival and activation. ß-Catenin is a multifunctional protein that stabilizes cell-cell interactions and regulates cell survival through its transcriptional activity. We used chronic lymphocytic leukemia (CLL) cells as a cellular model to study the role of ß-catenin in regulating the adhesion of tumor cells to their microenvironment, which is necessary for tumor cell survival and accumulation. When co-cultured with a stromal cell line (HS-5), a fraction of the CLL cells adhere to stromal cells in a dynamic fashion regulated by the different levels of ß-catenin expression. In non-adherent cells, ß-catenin is stabilized in the cytosol and translocates into the nucleus, increasing the expression of cyclin D1. In adherent cells, the level of cytosolic ß-catenin is low but membrane ß-catenin helps to stabilize the adhesion of CLL to stromal cells. Indeed, the overexpression of ß-catenin enhances the interaction of CLL with HS-5 cells, suggesting that this protein behaves as a regulator of cell adhesion to the stromal component and of the transcriptional regulation of cell survival. Inhibitors that block the stabilization of ß-catenin alter this equilibrium and effectively disrupt the support that CLL cells receive from the cross-talk with the stroma.


Assuntos
Tirosina Quinase da Agamaglobulinemia , Leucemia Linfocítica Crônica de Células B , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Comunicação Celular , Linhagem Celular Tumoral , Leucemia Linfocítica Crônica de Células B/patologia , Células Estromais/metabolismo , Microambiente Tumoral , Tirosina Quinase da Agamaglobulinemia/metabolismo
2.
Cell Signal ; 86: 110079, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252536

RESUMO

Vav1 exhibits two signal transducing properties as an adaptor protein and a regulator of cytoskeleton organization through its Guanine nucleotide Exchange Factor module. Although the expression of Vav1 is restricted to the hematopoietic lineage, its ectopic expression has been unraveled in a number of solid tumors. In this study, we show that in lung cancer cells, as such in hematopoietic cells, Vav1 interacts with the Spleen Tyrosine Kinase, Syk. Likewise, Syk interacts with ß-catenin and, together with Vav1, regulates the phosphorylation status of ß-catenin. Depletion of Vav1, Syk or ß-catenin inhibits Rac1 activity and decreases cell migration suggesting the interplay of the three effectors to a common signaling pathway. This model is further supported by the finding that in turn, ß-catenin regulates the transcription of Syk gene expression. This study highlights the elaborated connection between Vav1, Syk and ß-catenin and the contribution of the trio to cell migration.


Assuntos
Neoplasias Pulmonares , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-vav/genética , Transdução de Sinais , Quinase Syk/metabolismo
3.
Oncogene ; 39(14): 2934-2947, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32034308

RESUMO

B-cell receptor (BCR) signaling pathways and interactions with the tumor microenvironment account for mantle cell lymphoma (MCL) cells survival in lymphoid organs. In several MCL cases, the WNT/ß-catenin canonical pathway is activated and ß-catenin accumulates into the nucleus. As both BCR and ß-catenin are important mediators of cell survival and interaction with the microenvironment, we investigated the crosstalk between BCR and WNT/ß-catenin signaling and analyzed their impact on cellular homeostasis as well as their targeting by specific inhibitors. ß-catenin was detected in all leukemic MCL samples and its level of expression rapidly increased upon BCR stimulation. This stabilization was hampered by the BCR-pathway inhibitor Ibrutinib, supporting ß-catenin as an effector of the BCR signaling. In parallel, MCL cells as compared with normal B cells expressed elevated levels of WNT16, a NF-κB target gene. Its expression increased further upon BCR stimulation to participate to the stabilization of ß-catenin. Upon BCR stimulation, ß-catenin translocated into the nucleus but did not induce a Wnt-like transcriptional response, i.e., TCF/LEF dependent. ß-catenin rather participated to the regulation of NF-κB transcriptional targets, such as IL6, IL8, and IL1. Oligo pull down and chromatin immunoprecipitation experiments demonstrated that ß-catenin is part of a protein complex that binds the NF-κB DNA consensus sequence, strengthening the idea of an association between the two proteins. An inhibitor targeting ß-catenin transcriptional interactions hindered both NF-κB DNA recruitment and induced primary MCL cells apoptosis. Thus, ß-catenin likely represents another player through which BCR signaling impacts on MCL cell survival.


Assuntos
Linfoma de Célula do Manto/genética , NF-kappa B/genética , Receptores de Antígenos de Linfócitos B/genética , Transcrição Gênica/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Animais , Apoptose/genética , Linfócitos B/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/genética , Sobrevivência Celular/genética , Feminino , Células HEK293 , Homeostase/genética , Humanos , Camundongos , Fatores de Transcrição TCF/genética , Microambiente Tumoral/genética
4.
Int J Cancer ; 139(8): 1759-63, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27270786

RESUMO

TP53 abnormalities lead to resistance to purine analogues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL). At diagnosis, no more than 5% of patients carry the 17p deletion, most cases harbour mutations within the other TP53 allele. The incidence of a TP53 mutation as the only alteration is approximately 5%, but this depends on the sensitivity of the technique. Recently, having a complex karyotype has been considered a strong adverse prognostic factor. However, there are no longitudinal studies simultaneously examining the presence of the 17p deletion, TP53 mutations and karyotype abnormalities. We conducted a retrospective longitudinal study of 31 relapsed/refractory CLL patients. Two to six blood samples per patient were analyzed, with a median follow-up of 8 years. In this report, we assessed the sequence of events of TP53 clonal evolution and correlated the presence of TP53 abnormalities to genetic instability during progression and treatment. Next-generation sequencing allowed the early detection of TP53 mutated clones and was able to be performed on a routine basis, demonstrating an excellent correlation between the Illumina and Ion Torrent technologies. We concluded that TP53 mutations are early events and precede clonal evolution to complex karyotypes. We strongly recommend the early and iterated detection of TP53 mutations in progressive cases.


Assuntos
Genes p53 , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Proteína Supressora de Tumor p53/genética , Progressão da Doença , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/patologia , Estudos Longitudinais , Estudos Retrospectivos
5.
Oncotarget ; 6(4): 2524-37, 2015 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-25426554

RESUMO

Vav family members function as remarkable scaffold proteins that exhibit both GDP/GTP exchange activity for Rho/Rac GTPases and numerous protein-protein interactions via three adaptor Src-homology domains. The exchange activity is under the unique regulation by phosphorylation of tyrosine residues hidden by intra-molecular interactions. Deletion of the autoinhibitory N-terminal region results in an oncogenic protein, onco-Vav, leading to a potent activation of Rac GTPases whereas the proto-oncogene barely leads to transformation. Substitution of conserved residues of the SH2-SH3 adaptor region in onco-Vav reverses oncogenicity. While a unique substitution D797N did not affect transformation induced by onco-Vav, we demonstrate that this single substitution leads to transformation in the Vav1 proto-oncogene highlighting the pivotal role of the adaptor region. Moreover, we identified the cell junction protein ß-catenin as a new Vav1 interacting partner. We show that the oncogenicity of activated Vav1 proto-oncogene is associated with a non-degradative phosphorylation of ß-catenin at residues important for its functions and its redistribution along the cell membrane in fibroblasts. In addition, a similar interaction is evidenced in epithelial lung cancer cells expressing ectopically Vav1. In these cells, Vav1 is also involved in the modulation of ß-catenin phosphorylation. Altogether, our data highlight that only a single mutation in the proto-oncogene Vav1 enhances tumorigenicity.


Assuntos
Transformação Celular Neoplásica/genética , Mutação , Proteínas Proto-Oncogênicas c-vav/genética , Domínios de Homologia de src/genética , Animais , Antracenos/farmacologia , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Western Blotting , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Fibroblastos/metabolismo , Células HEK293 , Humanos , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Nus , Células NIH 3T3 , Fosforilação , Ligação Proteica , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-vav/metabolismo , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , beta Catenina/genética , beta Catenina/metabolismo
6.
Int J Cancer ; 136(12): 2761-74, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25388373

RESUMO

Several studies provide evidences for mantle cell lymphoma (MCL) cell survival relying on B-cell receptor (BCR)-mediated signalling pathways, whereas the nature of this activation is unknown. Significant progress in MCL treatment is achieved through therapies targeting BCR-associated kinases, i.e., Ibrutinib and Fostamatinib, inhibitors of BTK and SYK, respectively. Our study addresses survival signals emanating from the BCR or the tumour environment and how inhibiting BCR signalling effectors might impact these survival signals. We found that BTK was constitutively activated and that SYK phosphorylation was highly increased and sustained upon BCR activation of primary MCL cells. Moreover, MCL cells from leukaemic patients secreted high amount of IL-1ß, IL-6, IL-8 and CCL5. Activation of the BCR induced (i) cell survival, (ii) STAT3 activation and (iii) increased autocrine secretion of IL-1ß, IL-6, IL-8, CCL5, IL-10, TNFα and VEGF. Specific inhibition of BTK by Ibrutinib or SYK by Fostamatinib (R406) reversed these protective effects and decreased both basal and BCR-induced autocrine cytokine secretions associated with STAT3 phosphorylation. Interestingly, targeting BTK and SYK prevented and inhibited BCR-induced MCL cell adhesion to human bone marrow stromal cells (HMSCs) in short- and long-term co-culture. We demonstrated that BCR-induced survival relies on autocrine secretion of IL-1ß, TNFα and CCL5 that might facilitate adhesion of MCL cells to HMSC. Treatment with Ibrutinib or Fostamatinib blocked the chemotactic signal thus increasing apoptosis.


Assuntos
Oxazinas/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia , Idoso , Idoso de 80 Anos ou mais , Aminopiridinas , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Citocinas/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Morfolinas , Fosforilação/efeitos dos fármacos , Piperidinas , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Quinase Syk , Células Tumorais Cultivadas
7.
Methods Mol Biol ; 1054: 283-93, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23913300

RESUMO

Telomerase is the enzyme that extends the chromosome ends, thereby contributing to eukaryotic cell genome stability. Telomerase is expressed in the majority of cells that have an unlimited proliferation such as stem cells and cancer cells. The increased interest in telomerase in cancer research, challenged by the low cellular abundance of the enzyme, has led to the development of a reliable and at the same time very sensitive approach to detect telomerase activity. The telomeric repeat amplification protocol (TRAP) represents an easy and rapid method for detection of telomerase activity in cells. A non-telomeric TS primer is extended by telomerase in the first step followed by the PCR amplification of the products. The PCR step renders this protocol very sensitive to detect telomerase activity at the single cell level making it compatible with the analysis of tumor samples. When run on a polyacrylamide gel, the PCR product is a characteristic ladder of bands due to the repetitive nature of telomeric DNA sequence. The densitometric analysis of the ladder allows the TRAP assay to be used for comparative quantification of telomerase activity in different samples.


Assuntos
Eletroforese em Gel de Poliacrilamida/métodos , Reação em Cadeia da Polimerase/métodos , Sequências Repetitivas de Ácido Nucleico , Telomerase/química , Primers do DNA/química , Humanos , Telomerase/isolamento & purificação , Telômero/química
8.
Front Oncol ; 3: 146, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23772418

RESUMO

Telomeres are the terminal structures at the ends of linear chromosomes that represent a solution to the end replication problem. Specific binding of the six-protein subunit complex shelterin to telomeric, repetitive TTAGGG DNA sequences contributes to the stable architecture and maintenance of telomeres. Proteins involved in the DNA damage response are also localized at telomeres, and play a role in the surveillance and maintenance of telomere integrity. The enzyme responsible for telomere extension is telomerase, a ribonucleoprotein with reverse transcriptase activity. In the absence of telomerase, telomeres shorten to a length threshold that triggers the DNA damage response and replicative senescence. Here, we will summarize the latest findings concerning vertebrate telomere structure and epigenetics, and we present data regarding the impact of short telomeres upon cell signaling. In particular, in murine embryonic stem cells lacking telomerase, we found that distribution of cytosolic/nuclear ß-catenin, a key component of the Wnt signaling pathway, changes when telomeres become critically short. We discuss implications and future perspectives of the effect of epigenetic modifications and/or conformational changes of telomeres on cell metabolism and signaling networks. Such an analysis may unveil potential therapeutic targets for pathologies like cancer, where the integrity of telomeres is altered.

9.
Cell Stem Cell ; 12(4): 479-86, 2013 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-23561444

RESUMO

Functional telomeres are critical for stem cell proliferation; however, whether they are equally important for the stability of stem cell differentiation is not known. We found that mouse embryonic stem cells (ESCs) with critically short telomeres (Tert(-/-) ESCs) initiated normal differentiation after leukemia inhibitory factor (LIF) withdrawal but, unlike control ESCs, failed to maintain stable differentiation when LIF was reintroduced to the growth medium. Tert(-/-) ESCs expressed higher levels of Nanog and, overall, had decreased genomic CpG methylation levels, which included the promoters of Oct4 and Nanog. This unstable differentiation phenotype could be rescued by telomere elongation via reintroduction of Tert, via suppression of Nanog by small hairpin RNA (shRNA) knockdown, or via enforced expression of the de novo DNA methyltransferase 3b. These results demonstrate an unexpected role of functional telomeres in the genome-wide epigenetic regulation of cell differentiation and suggest a potentially important role of telomere instability in cell fate during development or disease.


Assuntos
Diferenciação Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Telômero/metabolismo , Animais , Ilhas de CpG/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Células-Tronco Embrionárias/enzimologia , Histonas/metabolismo , Proteínas de Homeodomínio/metabolismo , Lisina/metabolismo , Camundongos , Proteína Homeobox Nanog , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , DNA Metiltransferase 3B
10.
Nucleic Acids Res ; 40(5): e36, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22187156

RESUMO

Telomeres, the ends of linear chromosomes, safeguard against genome instability. The enzyme responsible for extension of the telomere 3' terminus is the ribonucleoprotein telomerase. Whereas telomerase activity can be reconstituted in vitro with only the telomerase RNA (hTR) and telomerase reverse transcriptase (TERT), additional components are required in vivo for enzyme assembly, stability and telomere extension activity. One such associated protein, dyskerin, promotes hTR stability in vivo and is the only component to co-purify with active, endogenous human telomerase. We used oligonucleotide-based affinity purification of hTR followed by native gel electrophoresis and in-gel telomerase activity detection to query the composition of telomerase at different purification stringencies. At low salt concentrations (0.1 M NaCl), affinity-purified telomerase was 'supershifted' with an anti-dyskerin antibody, however the association with dyskerin was lost after purification at 0.6 M NaCl, despite the retention of telomerase activity and a comparable yield of hTR. The interaction of purified hTR and dyskerin in vitro displayed a similar salt-sensitive interaction. These results demonstrate that endogenous human telomerase, once assembled and active, does not require dyskerin for catalytic activity. Native gel electrophoresis may prove useful in the characterization of telomerase complexes under various physiological conditions.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Eletroforese , Proteínas Nucleares/metabolismo , Telomerase/isolamento & purificação , Telomerase/metabolismo , Anticorpos , Proteínas de Ciclo Celular/imunologia , Linhagem Celular Tumoral , Humanos , Proteínas Nucleares/imunologia , Oligonucleotídeos , Cloreto de Sódio/química , Telomerase/análise
11.
Curr Biol ; 19(13): 1112-7, 2009 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-19540118

RESUMO

The Drosophila tumor suppressor gene fat encodes a large cadherin that regulates growth and a form of tissue organization known as planar cell polarity (PCP). Fat regulates growth via the Hippo kinase pathway, which controls expression of genes promoting cell proliferation and inhibiting apoptosis (reviewed in). The Hippo pathway is highly conserved and is implicated in the regulation of mammalian growth and cancer development. Genetic studies suggest that Fat activity is regulated by binding to another large cadherin, Dachsous (Ds). The tumor suppressor discs overgrown (dco)/Casein Kinase I delta/epsilon also regulates Hippo activity and PCP. The biochemical nature of how Fat, Ds, and Dco interact to regulate these pathways is poorly understood. Here we demonstrate that Fat is cleaved to generate 450 kDa and 110 kDa fragments (Fat(450) and Fat(110)). Fat(110) contains the cytoplasmic and transmembrane domain. The cytoplasmic domain of Fat binds Dco and is phosphorylated by Dco at multiple sites. Importantly, we show Fat forms cis-dimers and that Fat phosphorylation is regulated by Dachsous and Dco in vivo. We propose that Ds regulates Dco-dependent phosphorylation of Fat and Fat-associated proteins to control Fat signaling in growth and PCP.


Assuntos
Caderinas/metabolismo , Caseína Quinase 1 épsilon/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Sequência de Aminoácidos , Animais , Caderinas/genética , Caseína Quinase 1 épsilon/genética , Caseína Quinase Idelta/genética , Caseína Quinase Idelta/metabolismo , Moléculas de Adesão Celular/genética , Linhagem Celular , Polaridade Celular , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ligantes , Camundongos , Dados de Sequência Molecular , Fosforilação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transgenes
12.
Dev Cell ; 16(3): 411-20, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19289086

RESUMO

The Hippo kinase pathway plays a central role in growth regulation and tumor suppression from flies to man. The Hippo/Mst kinase phosphorylates and activates the NDR family kinase Warts/Lats, which phosphorylates and inhibits the transcriptional activator Yorkie/YAP. Current models place the FERM-domain protein Expanded upstream of Hippo kinase in growth control. To understand how Expanded regulates Hippo pathway activity, we used affinity chromatography and mass spectrometry to identify Expanded-binding proteins. Surprisingly we find that Yorkie is the major Expanded-binding protein in Drosophila S2 cells. Expanded binds Yorkie at endogenous levels via WW-domain-PPxY interactions, independently of Yorkie phosphorylation at S168, which is critical for 14-3-3 binding. Expanded relocalizes Yorkie from the nucleus, abrogating its nuclear activity, and it can regulate growth downstream of warts in vivo. These data lead to a new model whereby Expanded functions downstream of Warts, in concert with 14-3-3 proteins to sequester Yorkie in the cytoplasm, inhibiting growth activity of the Hippo pathway.


Assuntos
Proteínas de Drosophila/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transativadores/metabolismo , Motivos de Aminoácidos , Animais , Animais Geneticamente Modificados , Linhagem Celular , Citoplasma/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Modelos Biológicos , Proteínas Nucleares/genética , Ligação Proteica , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Transdução de Sinais , Transativadores/genética , Transfecção , Proteínas de Sinalização YAP
13.
Curr Biol ; 16(21): 2081-9, 2006 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-16996266

RESUMO

BACKGROUND: The tight control of cell proliferation and cell death is essential to normal tissue development, and the loss of this control is a hallmark of cancers. Cell growth and cell death are coordinately regulated during development by the Hippo signaling pathway. The Hippo pathway consists of the Ste20 family kinase Hippo, the WW adaptor protein Salvador, and the NDR kinase Warts. Loss of Hippo signaling in Drosophila leads to enhanced cell proliferation and decreased apoptosis, resulting in massive tissue overgrowth through increased expression of targets such as Cyclin E and Diap1. The cytoskeletal proteins Merlin and Expanded colocalize at apical junctions and function redundantly upstream of Hippo. It is not clear how they regulate growth or how they are localized to apical junctions. RESULTS: We find that another Drosophila tumor-suppressor gene, the atypical cadherin fat, regulates both cell proliferation and cell death in developing imaginal discs. Loss of fat leads to increased Cyclin E and Diap1 expression, phenocopying loss of Hippo signaling. Ft can regulate Hippo phosphorylation, a measure of its activation, in tissue culture. Importantly, fat is needed for normal localization of Expanded at apical junctions in vivo. Genetic-epistasis experiments place fat with expanded in the Hippo pathway. CONCLUSIONS: Together, these data suggest that Fat functions as a cell-surface receptor for the Expanded branch of the conserved Hippo growth control pathway.


Assuntos
Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/fisiologia , Proliferação de Células , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiologia , Drosophila/genética , Genes Supressores de Tumor , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Animais , Apoptose , Caderinas/genética , Caderinas/fisiologia , Ciclina E/metabolismo , Drosophila/crescimento & desenvolvimento , Drosophila/fisiologia , Olho/embriologia , Proteínas Inibidoras de Apoptose/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Processamento Pós-Transcricional do RNA
14.
Proteomics ; 2(7): 850-6, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12124930

RESUMO

Human butyrophilin (BTN) expression in milk fat globule (MFGM) was evaluated using two dimensional electrophoresis (2-DE) as the separation technique, and peptide mass mapping by matrix-assisted laser desorption/ionisation-mass spectrometry (MALDI-MS) as the identification tool. Since milk composition changes throughout lactation time, 2-DE maps in the pH range 4-7 of colostral MFGM and mature MFGM were compared, showing only slight differences in BTN spot distribution. The BTN gene family codes for seven proteins (BTN, BTN2A1, BTN2A2, BTN2A3, BTN3A1, BTN3A2, BTN3A3), their presence in human tissues has to date been evaluated only at a transcriptional level. Among 70 spots, analyzed and identified by MALDI-MS, 13 spots were identified as BTN spots and only one as a fragment of BTN2A1. BTN was present in multiple glycoforms, and two smaller BTN forms of about 45 kDa were also identified. We propose an array of BTNs on human MFGM, which could provide breast-fed infants with immune molecules during the neonatal period.


Assuntos
Gorduras/química , Membranas Intracelulares/química , Glicoproteínas de Membrana/genética , Leite Humano/química , Proteômica , Sequência de Aminoácidos , Animais , Butirofilinas , Vesículas Citoplasmáticas/química , Vesículas Citoplasmáticas/metabolismo , Eletroforese em Gel Bidimensional , Feminino , Humanos , Membranas Intracelulares/metabolismo , Espectrometria de Massas , Dados de Sequência Molecular , Família Multigênica , Alinhamento de Sequência
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