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1.
Ukr Biokhim Zh (1999) ; 82(4): 18-32, 2010.
Artigo em Ucraniano | MEDLINE | ID: mdl-21516713

RESUMO

Recent scientific research demonstrates that protein kinases of PKD family affect biological features of normal and malignant cells. Differential expression of PKD genes was found in tumors of different histogenesis. These protein kinases could be activated by growth factors, antigen stimulation, and oxidative stress, the processes that usually can be observed during tumor progression. PKD regulate cell-cell contacts by affecting cell adhesion. PKD are involved in the regulation of cell proliferation and apoptosis, and also participate in epigenetic regulation of gene expression. That is why studies of differential expression and activity of PKD1, PKD2 and PKD3 in the context of tumor spreading and prognosis could be the perspective subject of translational research in oncology. This will contribute to the development of new approaches to differential diagnostics of tumor and target therapy, and also reveal prognostic factors for the prediction of clinical outcome.


Assuntos
Pesquisa Biomédica/métodos , Oncologia/métodos , Neoplasias/enzimologia , Proteína Quinase C/fisiologia , Animais , Apoptose , Pesquisa Biomédica/tendências , Adesão Celular , Sobrevivência Celular , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Oncologia/tendências , Neoplasias/patologia , Proteína Quinase C/genética , Proteína Quinase C/metabolismo
2.
Ukr Biokhim Zh (1999) ; 80(4): 16-24, 2008.
Artigo em Ucraniano | MEDLINE | ID: mdl-19140446

RESUMO

The new family of serine/threonine protein kinases D (PKD) belongs to Ca2+/calmodulin-dependent protein kinase group. Here we review with the role of PKDs in the regulation of post-translational modification of cellular proteins. PKDs directly phosphorylate a number of cell signaling molecules, moreover PKDs indirectly regulate histone acetylation and glycosylation of proteins. The protein kinases of PKD family control physiologic cell processes, such as apoptosis, regulation of immune signaling, proliferation, adhesion and motility of cells, transmission of signals during oxidative stress. PKDs modulate signaling cascades, which are associated with ERK and JNK protein kinases, stress initiated activation of NF-kappaB. PKD dependent post-translational modifications are linked to chromatin organization, epigenetic regulation of gene expression, and also to regulation of Golgi apparatus structure and function.


Assuntos
Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Apoptose/fisiologia , Fenômenos Fisiológicos Celulares , Humanos , Fosforilação , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Especificidade por Substrato
3.
Exp Oncol ; 28(3): 225-30, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17080017

RESUMO

AIM: To study the PKD2 expression, autophosphorylation and localization in reactive lymph nodes and tumors of lymphoid tissues. MATERIALS AND METHODS: Specific antibodies, which recognize PKD1/2 or PKD2 and autophosphorylated PKD1/2, were used for immunohistochemical and biochemical studies of tonsils, reactive lymph nodes, tumor samples of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). RESULTS: Immunohistochemical and biochemical analysis of PKD1 and PKD2 expression showed PKD2 expression in tonsils, reactive lymph nodes and tumor tissues from patients with NHL and HL. Furthermore, we were not able to reveal PKD1 expression in studied lymphoid tissues. In tonsils and reactive lymph nodes the PKD2 expression was detected in T and B cell zones with highest level in germinal centers of lymphoid follicles and the maximum level of autophosphorylation in the light zones of the germinal centers. We found that low level of PKD2 expression and autophosphorylation was characteristic feature for mantle cell lymphomas, Burkitt's lymphomas, and in 50% of CLL/small lymphocytic lymphomas. Lymphoma cells of germinal center origin and with activated B cell phenotype (diffuse large B cell lymphomas, HL) and anaplastic large cells lymphoma demonstrated the high level of PKD2 expression and autophosphorylation. CONCLUSIONS: The level of PKD2 expression and autophosphorylation in neoplastic cells corresponds to the expression pattern of this kinase in their normal analogs, and to the level of cell differentiation and activation.


Assuntos
Doença de Hodgkin/enzimologia , Linfoma não Hodgkin/enzimologia , Proteínas Quinases/análise , Doença de Hodgkin/patologia , Humanos , Imuno-Histoquímica , Linfonodos/enzimologia , Linfoma não Hodgkin/patologia , Tonsila Palatina/enzimologia , Fosforilação , Proteína Quinase C/análise , Proteína Quinase D2
4.
J Immunol ; 166(9): 5480-7, 2001 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11313386

RESUMO

CD150 (SLAM/IPO-3) is a cell surface receptor that, like the B cell receptor, CD40, and CD95, can transmit positive or negative signals. CD150 can associate with the SH2-containing inositol phosphatase (SHIP), the SH2-containing protein tyrosine phosphatase (SHP-2), and the adaptor protein SH2 domain protein 1A (SH2D1A/DSHP/SAP, also called Duncan's disease SH2-protein (DSHP) or SLAM-associated protein (SAP)). Mutations in SH2D1A are found in X-linked lymphoproliferative syndrome and non-Hodgkin's lymphomas. Here we report that SH2D1A is expressed in tonsillar B cells and in some B lymphoblastoid cell lines, where CD150 coprecipitates with SH2D1A and SHIP. However, in SH2D1A-negative B cell lines, including B cell lines from X-linked lymphoproliferative syndrome patients, CD150 associates only with SHP-2. SH2D1A protein levels are up-regulated by CD40 cross-linking and down-regulated by B cell receptor ligation. Using GST-fusion proteins with single replacements of tyrosine at Y269F, Y281F, Y307F, or Y327F in the CD150 cytoplasmic tail, we found that the same phosphorylated Y281 and Y327 are essential for both SHP-2 and SHIP binding. The presence of SH2D1A facilitates binding of SHIP to CD150. Apparently, SH2D1A may function as a regulator of alternative interactions of CD150 with SHP-2 or SHIP via a novel TxYxxV/I motif (immunoreceptor tyrosine-based switch motif (ITSM)). Multiple sequence alignments revealed the presence of this TxYxxV/I motif not only in CD2 subfamily members but also in the cytoplasmic domains of the members of the SHP-2 substrate 1, sialic acid-binding Ig-like lectin, carcinoembryonic Ag, and leukocyte-inhibitory receptor families.


Assuntos
Proteínas de Transporte/fisiologia , Glicoproteínas/metabolismo , Imunoglobulinas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Domínios de Homologia de src/imunologia , Sequência de Aminoácidos , Antígenos CD , Linfócitos B/enzimologia , Linfócitos B/metabolismo , Proteínas de Transporte/biossíntese , Proteínas de Transporte/metabolismo , Linhagem Celular Transformada , Células Cultivadas , Citoplasma/imunologia , Citoplasma/metabolismo , Glicoproteínas/genética , Humanos , Imunoglobulinas/genética , Células Jurkat , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Ligação Proteica/genética , Ligação Proteica/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteína Tirosina Fosfatase não Receptora Tipo 6 , Receptores de Superfície Celular , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Tirosina Fosfatases Contendo o Domínio SH2 , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária , Células Tumorais Cultivadas , Tirosina/genética
5.
Appl Biochem Biotechnol ; 83(1-3): 255-68; discussion 268-9, 297-313, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10826965

RESUMO

The cytotoxicity of DNA-specific autoantibodies from sera of patients with systemic lupus erythematosis (SLE) and with lymphoproliferative diseases, and from blood of healthy donors was examined on tumor-cell lines L929 and HL-60. DNA-binding IgG fractions from SLE and chronic lymphocytic leukemia (CLL) sera were cytotoxic at concentrations of up to 10(-10) M. No detectable changes in cell viability were observed after incubation with antibodies devoid of DNA-binding activity and DNA-specific antibodies isolated from blood of healthy donors and patients with T-cell lymphoma, B-cell lymphosarcoma, and acute B-cell leukemia. There was good correlation between the cytotoxic activity and DNA-hydrolyzing activity of anti-DNA antibodies. The cytotoxic effect of DNA-binding antibodies presumably was complement-independent, because it was attributed only to the Fab fragment. The cytotoxic effect was completely inhibited by preincubation with double-stranded DNA (dsDNA). Both the cytotoxic effect and the DNA-hydrolyzing activity of anti-DNA antibodies were significantly increased in the antibody fraction that displayed cross-reactivity with nuclear matrix proteins. Possible mechanisms for the formation and pathogenicity of cytotoxic anti-DNA antibodies are discussed in this article.


Assuntos
Anticorpos Antinucleares/metabolismo , Anticorpos Catalíticos/metabolismo , Citotoxicidade Imunológica , DNA/imunologia , DNA/metabolismo , Anticorpos Antinucleares/sangue , Anticorpos Catalíticos/sangue , Reações Cruzadas , Células HL-60 , Humanos , Hidrólise , Fragmentos de Imunoglobulinas/sangue , Fragmentos de Imunoglobulinas/metabolismo , Imunoglobulina G/sangue , Imunoglobulina G/metabolismo , Técnicas In Vitro , Lúpus Eritematoso Sistêmico/imunologia , Transtornos Linfoproliferativos/imunologia , Membrana Nuclear/imunologia , Matriz Nuclear/imunologia , Células Tumorais Cultivadas
6.
J Immunol ; 162(10): 5719-27, 1999 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-10229804

RESUMO

CDw150, a receptor up-regulated on activated T or B lymphocytes, has a key role in regulating B cell proliferation. Patients with X-linked lymphoproliferative disease have mutations in a gene encoding a protein, DSHP/SAP, which interacts with CDw150 and is expressed in B cells. Here we show that CDw150 on B cells associates with two tyrosine-phosphorylated proteins, 59 kDa and 145 kDa in size. The 59-kDa protein was identified as the Src-family kinase Fgr. The 145-kDa protein is the inositol polyphosphate 5'-phosphatase, SH2-containing inositol phosphatase (SHIP). Both Fgr and SHIP interact with phosphorylated tyrosines in CDw150's cytoplasmic tail. Ligation of CDw150 induces the rapid dephosphorylation of both SHIP and CDw150 as well as the association of Lyn and Fgr with SHIP. CD95/Fas-mediated apoptosis is enhanced by signaling via CDw150, and CDw150 ligation can override CD40-induced rescue of CD95-mediated cell death. The ability of CDw150 to regulate cell death does not correlate with serine phosphorylation of the Akt kinase, but does correlate with SHIP tyrosine dephosphorylation. Thus, the CDw150 receptor may function to regulate the fate of activated B cells via SHIP as well as via the DSHP/SAP protein defective in X-linked lymphoproliferative disease patients.


Assuntos
Apoptose , Linfócitos B/metabolismo , Glicoproteínas/metabolismo , Imunoglobulinas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Serina-Treonina Quinases , Receptor fas/metabolismo , Antígenos CD , Proteínas de Transporte/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Transtornos Linfoproliferativos/imunologia , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Ligação Proteica , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Agregação de Receptores , Receptores de Superfície Celular , Transdução de Sinais , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária , Domínios de Homologia de src , Quinases da Família src
7.
Appl Biochem Biotechnol ; 47(2-3): 305-14; discussion 314-5, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7944345

RESUMO

Sera of patients with different types of leukemia and acquired immune deficiency syndrome (AIDS) have been examined for the presence of the anti-DNA antibodies. DNA-hydrolyzing activity of antibodies was detected in the sera of patients with chronic lymphoid leukemia (CLL), pre-B-cell acute lymphoid leukemia (pre-B-All), acute myeloleukosis (AML), and AIDS in stages III and IV of the disease. In immunofluorescence tests, the DNA-hydrolyzing antibodies reacted preferentially with proliferating cell nuclei compared with resting cells. A 35-kDa factor was identified as the target for the DNA antibodies in the cell nuclei. The DNA-hydrolyzing antibody fraction from the serum of an AIDS patient crossreacted with HIV I virus proteins gp160, gp120, and p65.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Anticorpos Catalíticos/metabolismo , Autoanticorpos/metabolismo , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Leucemia/imunologia , Anticorpos Catalíticos/imunologia , Autoanticorpos/imunologia , Divisão Celular , Reações Cruzadas , Eletroforese em Gel de Poliacrilamida , Citometria de Fluxo , Imunofluorescência , Produtos do Gene pol/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Hidrólise , Proteínas de Neoplasias , Sialoglicoproteínas/imunologia , Células Tumorais Cultivadas , Produtos do Gene pol do Vírus da Imunodeficiência Humana
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