Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P67775 (alpha isoform)
 797 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated intraepithelial T cells from the small intestine, SI (jejunum, ileum) and the large intestine, LI (colon) of euthymic (BALB/c, H-2d; C.B-17+/+, H-2d; C57BL/6, H-2b) and athymic (C57BL/6 nu/nu; BNX bg/bg nu/nu xid/xid) mice. From individual euthymic and athymic mice, 7 x 10(6) intraepithelial lymphocytes (IEL) per mouse were isolated from the SI. Ten-fold lower numbers of IEL were obtained from the LI epithelium (4 x 10(5) IEL per mouse). Thymus-dependent and -independent T cells represented > 80% of SI-IEL but the fraction of T cells was reduced from 20% to 40% in LI-IEL. In euthymic mice, alpha beta T cells predominated in SI-IEL and in particular in LI-IEL populations, while SI-IEL and LI-IEL populations of athymic mice contained predominantly gamma delta T cells. The intraepithelial T cell subset distribution was different in SI versus LI: mainly CD8+ T cells were present in the SI, but a large CD4+ T cell subset was present in the LI. 'Double positive' CD4+ CD8 alpha+ T cells were present mainly in the SI epithelium but were rare in the LI epithelium. In euthymic as well as athymic mice, T cells expressing the homodimeric CD8 alpha alpha isoform predominated in the SI epithelium, while T cells expressing the heterodimeric CD8 alpha beta isoform predominated in the LI epithelium. LI-derived TCR alpha beta+ IEL displayed the CD2+ CD28+ LPAM-1/2- M290+ phenotype, and a fraction of them expressed the L-selectin LECAM-1. In contrast, a large fraction of TCR alpha beta+ SI-IEL was CD2- CD28- LPAM-1/2- M290+ and LECAM-1-. RAG-1/2 expression was detectable by RT-PCR in IEL from the SI but not the LI. Striking differences in phenotype were thus apparent between thymus-dependent and thymus-independent T cells in the epithelial layer of the jejunum/ileum and the colon of the mouse.
 ...
PMID:Regional specialization of intraepithelial T cells in the murine small and large intestine. 786 56

Peritoneal lymphocytes (PCL) of 45 healthy individuals, four uremic patients with end-stage renal disease (ESRD) and 25 long-term continuous ambulatory peritoneal dialysis (CAPD) patients were characterized by flow cytometry to investigate whether CAPD alters the phenotype of PCL. B lineage cells constitute a minority of PCL (2.5% of cells). Although the majority of peritoneal T cells expressed alpha beta T cell receptor (TcR), 7% expressed gamma delta TcR, a proportion which was significantly higher than that in peripheral blood (PBMC) (approximately 4%). The majority of PCL T cells exhibited markers of the thymus-dependent lineage (CD2, CD3, TcR alpha beta, CD8 alpha beta or CD4) and surface antigens associated with memory and activation (CD45RO, CD11a, CD18, CD49d, HLA-DR). An average of 75% of both CD4+ and CD8+ PCL T cells of healthy subjects and CAPD patients were CDw60+, thus characterizing the T cell subset containing the helper activity for the mitogen-driven B cell differentiation. CD44s was abundantly expressed on PCL T cells. In contrast to PCL T cells of healthy subjects peritoneal T lymphocytes of CAPD patients exhibited CD44 splice variants containing products of exon-v9 and the proportion of CD44v9+ cells correlated with the frequency of peritonitis episodes the patients had gone through. The majority of PCL T cells of both healthy subjects and CAPD patients were CD8+. A large proportion of CD8+ PCL T cells from healthy subjects expressed the homodimeric CD8 alpha alpha isoform; however, such cells were not found in CAPD patients. In healthy subjects mRNA for the recombination activating gene 1 (RAG-1) was detectable in a PCL population containing CD7-CD34+ and CD7+CD34+ cells. In contrast, neither mRNA transcripts of the RAG-1 gene nor CD34+ cells were detectable in PCL of CAPD patients.
 ...
PMID:Continuous ambulatory peritoneal dialysis impairs T lymphocyte selection in the peritoneum. 873 Nov 4

A novel member of the epidermal growth factor (EGF) family, the neural- and thymus-derived activator for ErbB kinases (NTAK), has been purified and cloned. Five alternative spliced isoforms have been detected in the rat adrenal pheochromocytoma cell line, PC-12 cells. The rat NTAK alpha2a isoform exhibits 94% identity in its primary sequence with the human NTAK alpha isoform. In vivo, NTAK is only expressed in the brain of rat E11.5 embryos, and in the brain and thymus of adult rats. The soluble 46 kDa form binds directly to ErbB3 and B4, but not to ErbB1 or B2. NTAK, however, transactivates ErbB1 and B2 via heterodimerization with ErbB3 or B4. NTAK stimulates the differentiation of MDA-MB-453 cells and competitively inhibits the binding of [125I]neuregulin to these cells. In addition to these neuregulin-like properties, NTAK exhibits limited structural homology to neuregulins in the immunoglobulin (Ig)-like, EGF-like, and hydrophobic domains. Thus, NTAK appears to be a new member of the EGF family displaying neuregulin properties.
 ...
PMID:A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4. 934 1

Alternative splicing of the human glucocorticoid receptor (hGR) primary transcript produces two highly homologous protein isoforms, termed hGR alpha and hGRbeta, that differ at their carboxy-termini. In contrast to the well characterized hGR alpha isoform, which modulates gene expression in a hormone-dependent fashion, the biological significance of hGRbeta has only recently begun to emerge. We and others have shown that the hGRbeta messenger RNA transcript is widely expressed in human tissues and that the hGRbeta protein functions as a dominant negative inhibitor of hGR alpha in transfected cells. Unfortunately, these initial studies did not determine whether the hGRbeta protein was made in vivo. Such analyses are hindered because available anti-hGR antibodies cannot discriminate between the similarly sized hGR alpha and hGRbeta proteins. Therefore, to investigate the expression of the hGRbeta protein, we have produced an antipeptide, hGRbeta-specific antibody termed BShGR. This antibody was made against the unique 15-amino acid peptide at the carboxy-terminus of hGRbeta and recognizes both the native and denatured conformations of hGRbeta, but does not cross-react with hGR alpha. Using BShGR on Western blots and in immunoprecipitation experiments, we detected the hGRbeta protein in a variety of human cell lines and tissues. Immunocytochemistry was then performed with BShGR on HeLa S3 and CEM-C7 cells and on tissue sections prepared from lung, thymus, and liver to assess the cellular and subcellular distribution of hGRbeta. In all immunopositive cells, hGRbeta was found in the nucleus independent of glucocorticoid treatment. Within tissues, the hGRbeta protein was expressed most abundantly in the epithelial cells lining the terminal bronchiole of the lung, forming the outer layer of Hassall's corpuscle in the thymus, and lining the bile duct in the liver. As a potential in vivo inhibitor of hGR alpha activity, expression of hGRbeta may be an important factor regulating target cell responsiveness to glucocorticoids.
 ...
PMID:Expression and subcellular distribution of the beta-isoform of the human glucocorticoid receptor. 934 35

The protein phosphatase calcineurin is known to be an essential intracellular signal transducer involved in the TCR-mediated signal transduction pathway and is the common target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. The catalytic subunit of calcineurin exists in multiple isoforms, but their functional differences are not known. It has been assumed that the alpha isoform of calcineurin is the relevant isoform mediating TCR signaling. Recently, calcineurin alpha was knocked out in mice, but no defect in the TCR-mediated IL-2 production was observed, suggesting that another isoform of calcineurin mediates the TCR signal transduction pathway. We have generated specific polyclonal antibodies against the alpha and the beta2 isoforms of calcineurin and examined their distribution in murine tissues and immune cells by immunohistochemical staining and Western blot analysis. We found that the beta2 isoform of calcineurin is predominant in T and B lymphocytes as well as in thymus compared to the alpha isoform, suggesting that the beta2 isoform may play a key role in TCR signaling. Furthermore, we observed that the two isoforms exhibit distinct expression patterns in both kidney and thymus, indicating that the two isoforms of calcineurin have distinct cellular functions. Together, these findings raise the possibility that the nephrotoxicity associated with CsA and FK506 can be reduced by designing novel inhibitors of calcineurin that target specific isoforms of the enzyme.
 ...
PMID:Distinct tissue and cellular distribution of two major isoforms of calcineurin. 939 69

Paxillin, a focal adhesion protein, exists as multiple isoforms in humans (alpha, beta, and gamma). To understand more about the physiological role of each isoform, we have employed the mouse system. We found that although the alpha and beta isoforms are present in the mouse, the gamma isoform is not. The alpha isoform protein was detected clearly in most adult tissues, whereas the beta isoform protein was almost undetectable except in spleen, testis, thymus, and lung. On the other hand, mRNAs of both isoforms were detectable in all tissues we examined. High levels of the beta isoform protein was detected in peritoneal exudate macrophage cells in adult mouse as well as in cultured fibroblasts, together with the alpha isoform. The alpha isoform was expressed at a constant level throughout the embryonic stages we examined, whereas the beta isoform protein was detected at the mid-stages of development and increased to levels almost equal to those of the alpha isoform during the late stages of embryogenesis. Therefore, unlike the alpha isoform, expression of the beta isoform protein is restricted in adult tissues. Moreover, we showed that alpha and beta isoforms were colocalized within the same focal adhesion plaques, and cytoplasmic pools of both isoforms exist in the perinuclear area, colocalized with the Golgi apparatus.
 ...
PMID:Paxillin isoforms in mouse. Lack of the gamma isoform and developmentally specific beta isoform expression. 971 67

A novel member of the epidermal growth factor (EGF) family, the neural and thymus-derived activator for ErbB kinase (NTAK) has been cloned from the cDNA library of a rat pheochromocytoma cell line, PC12 cells and human neuroblastoma cell line, SK-N-SH cells. Four alternative spliced isoforms from rat cDNA have been detected by the methods of RT-PCR. The rat NTAK alpha 2a isoform exhibits 94% identity in its sequence with the human NTAK alpha isoform. Three characteristic Ig-like, EGF-like and hydrophobic domains have been identified in rat and human NTAK molecules. Recombinant NTAK, the soluble 46 kDa form, binds directly to ErbB3 and ErbB4, but not ErbB1 and B2. NTAK, however, transactivates with heterodimer such as ErbB1/B3, B1/B4, B2/B3, B2/B4, and B3/B4. NTAK stimulates the differentiation of MDA-MB-453 cells, derived from blast carcinoma. NTAK competitively inhibits the binding of [125I] NRG-1 to these cells. Thus, NTAK is a new member of the EGF family displaying NRG-1 properties.
 ...
PMID:[Structure and function of a novel ErbB ligand, NTAK]. 986 30

A murine alpha4, identified in lymphocytes, binds to protein phosphatase 2A (PP2A). We found another murine alpha4-related gene (named alpha4-b) expressed selectively in the brain and testis. The alpha4-b transcript is expressed in the brain and testis, but is not detected in the spleen, thymus, bone marrow, liver, kidney, lung, heart or muscle. In-situ RNA hybridization analysis suggested that alpha4-b is expressed in most neuronal cells in the brain, but it is not expressed in the glial cells. The alpha4-b cDNA encodes a putative protein that is highly homologous (66% identity in amino-acid sequence) to the alpha4 molecule. The alpha4-b protein associates with the catalytic subunit of PP2A (PP2Ac), suggesting that the alpha4-b protein is involved in the regulation of phosphatase activity in neuronal cells.
 ...
PMID:A new member of the alpha4-related molecule (alpha4-b) that binds to the protein phosphatase 2A is expressed selectively in the brain and testis. 1049 Nov 15

Using a subtractive cDNA cloning strategy, we isolated previously five novel genes that were expressed abundantly by the murine dendritic cell (DC) line XS52, but not by the J774 macrophage line. One of these genes encoded a unique, DC-associated C-type lectin, termed "dectin-1." Here we report the characterization of a second novel gene that was also expressed in a DC-specific manner. Clone 1B12 encoded a type II membrane-integrated polypeptide of 209 amino acids containing a single carbohydrate recognition domain motif in the COOH terminus. The expression pattern of this molecule, termed "dectin-2," was almost indistinguishable from that for dectin-1; that is, both were expressed abundantly at mRNA and protein levels by the XS52 DC line, but not by non-DC lines, and both were detected in spleen and thymus, as well as in skin resident DC (i.e. Langerhans cells). Interestingly, reverse transcriptase-polymerase chain reaction and immunoblotting revealed multiple bands of dectin-2 transcripts and proteins suggesting molecular heterogeneity. In fact, we isolated additional cDNA clones encoding two distinct, truncated dectin-2 isoforms. Genomic analyses indicated that a full-length dectin-2 (alpha isoform) is encoded by 6 exons, whereas truncated isoforms (beta and gamma) are produced by alternative splicing. We propose that dectin-2 and its isoforms, together with dectin-1, represent a unique subfamily of DC-associated C-type lectins.
 ...
PMID:Cloning of a second dendritic cell-associated C-type lectin (dectin-2) and its alternatively spliced isoforms. 1076 25

NTAK (neural- and thymus-derived activator for the ErbB kinase, neuregulin-2) is a novel member of the epidermal growth factor (EGF) family. We have isolated and characterized the human NTAK gene, comprising 12 exons spanning in excess of 55 kilobases (kb). The 7. 0kb long mRNA of the human NTAK gene was expressed in the human neuroblastoma SK-N-SH cell line with two alternative isoforms detected. Furthermore, six isoforms have been identified from rat brain and PC-12 cells. Although the alpha isoform of the NTAK gene was found to be expressed in all tissues including brain, the beta isoform was expressed only in rat brain tissues. Potential regulatory regions included consensus binding sites for AP-2, TF-IIIA, Sp-1, and YY-1 located in the 5'-flanking region of the NTAK gene.
 ...
PMID:Characterization of the human NTAK gene structure and distribution of the isoforms for rat NTAK mRNA. 1097 60


1 2 Next >>