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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell adhesion molecule-like tyrosine phosphatase CRYPalpha is localized on retinal axons and their growth cones. We present evidence that two isoforms of this type IIa phosphatase, CRYPalpha1 and CRYPalpha2, have extracellular ligands along the developing retinotectal pathway. Using alkaline phosphatase fusion proteins containing the CRYPalpha1 ectodomain, we detect a prominent ligand on basement membranes of the early retina, optic stalk, and chiasm. A second ligand is observed in the endfeet region of radial processes in the developing stratum opticum, the site of initial retinal axon invasion. This latter ligand binds CRYPalpha2 preferentially. Further ligand interactions are detected for both CRYPalpha protein isoforms in retinorecipient tectal laminae and on retinal fibers themselves. CRYPalpha thus has cell- and matrix-associated ligands along the entire retinotectal projection. Moreover, these ligands appear to be heterotypic and interact with CRYPalpha through both its immunoglobulin and fibronectin type III regions. The anteroposterior levels of the ligands are relatively uniform within the retina and tectum, suggesting that the CRYPalpha protein within retinal axons does not directly recognise topographically graded guidance cues. We propose that CRYPalpha may have a permissive role in promoting retinal axon growth across the eye and tectum and that its functions are modulated temporally and spatially by isoform-specific interactions with cell- and matrix-associated ligands.
Mol Cell Neurosci 1999 Sep
PMID:Retinotectal ligands for the receptor tyrosine phosphatase CRYPalpha. 1049 24

Appropriate regulation of tyrosine phosphorylation is essential for axon growth and guidance; evidence from invertebrates indicates that receptor-type tyrosine phosphatases (RPTPs) are required for correct axon growth during CNS development. One vertebrate RPTP, PTP-delta, is highly expressed in brain and has a cell adhesion molecule-like extracellular domain (ECD) comprising three immunoglobulin repeats and eight fibronectin type III repeats. Using fluorescent beads (Covaspheres) coated with the PTP-delta ECD, as well as insect cells expressing PTP-delta on their surfaces, we show that PTP-delta is a homophilic cell adhesion molecule. A variety of chick neurons adhere strongly to an Fc fusion protein containing the PTP-delta ECD. Additionally, substrate-bound PTP-delta ECD fusion protein strongly promotes neurite outgrowth from forebrain neurons; this effect is separable from its effect on adhesion. Our results indicate that PTP-delta is a neurite-promoting cell adhesion molecule for CNS neurons.
Mol Cell Neurosci
PMID:Receptor tyrosine phosphatase-delta is a homophilic, neurite-promoting cell adhesion molecular for CNS neurons. 1058 91

Associations between plasma membrane-linked proteins and the actin cytoskeleton play a crucial role in defining cell shape and determination, ensuring cell motility and facilitating cell-cell or cell-substratum adhesion. Here, we present evidence that CEACAM1-L, a cell adhesion molecule of the carcinoembryonic antigen family, is associated with the actin cytoskeleton. We have delineated the regions involved in actin cytoskeleton association to the distal end of the CEACAM1-L long cytoplasmic domain. We have demonstrated that CEACAM1-S, an isoform of CEACAM1 with a truncated cytoplasmic domain, does not interact with the actin cytoskeleton. In addition, a major difference in subcellular localization of the two CEACAM1 isoforms was observed. Furthermore, we have established that the localization of CEACAM1-L at cell-cell boundaries is regulated by the Rho family of GTPases. The retention of the protein at the sites of intercellular contacts critically depends on homophilic CEACAM1-CEACAM1 interactions and association with the actin cytoskeleton. Our results provide new evidence on how the Rho family of GTPases can control cell adhesion: by directing an adhesion molecule to its proper cellular destination. In addition, these results provide an insight into the mechanisms of why CEACAM1-L, but not CEACAM1-S, functions as a tumor cell growth inhibitor.
Mol Biol Cell 2000 Jan
PMID:The CEACAM1-L glycoprotein associates with the actin cytoskeleton and localizes to cell-cell contact through activation of Rho-like GTPases. 1063 91

Nectin-2 is a cell adhesion molecule encoded by a member of the poliovirus receptor gene family. This family consists of human, monkey, rat, and murine genes that are members of the immunoglobulin gene superfamily. Nectin-2 is a component of cell-cell adherens junctions and interacts with l-afadin, an F-actin-binding protein. Disruption of both alleles of the murine nectin-2 gene resulted in morphologically aberrant spermatozoa with defects in nuclear and cytoskeletal morphology and mitochondrial localization. Homozygous null males are sterile, while homozygous null females, as well as heterozygous males and females, are fertile. The production by nectin-2(-/-) mice of normal numbers of spermatozoa containing wild-type levels of DNA suggests that Nectin-2 functions at a late stage of germ cell development. Consistent with such a role, Nectin-2 is expressed in the testes only during the later stages of spermatogenesis. The structural defects observed in spermatozoa of nectin-2(-/-) mice suggest a role for this protein in organization and reorganization of the cytoskeleton during spermiogenesis.
Mol Cell Biol 2000 Apr
PMID:Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions. 1073 89

The myelin-associated glycoprotein (MAG) is a cell adhesion molecule expressed by myelinating glia, existing as two isoforms that differ only by their cytoplasmic domains. We have studied the in vitro phosphorylation of recombinant rat MAG cytoplasmic domains by three kinases for which consensus sequences exist within this domain, revealing phosphorylation of the L-MAG-specific domain by protein kinase A (PKA). Phosphorylation of the L-MAG cytoplasmic domain by PKA was decreased in the presence of S100beta, providing a functional significance to the interaction between L-MAG and S100beta, and further indicating that L-MAG may play a role in myelinating glial cell signalling processes.
Brain Res Mol Brain Res 2000 Mar 29
PMID:S100beta inhibits the phosphorylation of the L-MAG cytoplasmic domain by PKA. 1076 18

Recently, we developed a novel molecular approach, CD44 v8-10/CD44 v10 competitive reverse transcription-polymerase chain reaction (CC-RT-PCR), to detect a sparse population of cancer cells overexpressing CD44v8-10 among a much larger population of nonneoplastic cells in body fluids by the measurement of the transcriptional level of CD44v8-10 relative to that of CD44v10. We have shown the utility of CC-RT-PCR in diagnosing disease using urine samples from patients with bladder cancer. In this study, we initially examined the expression of CD44 splice variants in human upper urinary tract transitional-cell carcinomas (UUT-TCCs) and their adjacent normal urinary tissues by RT-PCR. Any CD44 variant isoforms were barely detectable in normal urinary tissues, whereas CD44v8-10 was predominantly expressed in 21 of the 25 UUT-TCC specimens (84%). We then applied CC-RT-PCR to spontaneously voided urine samples from 40 patients with UUT-TCC and 40 patients with benign urologic diseases. The CC-RT-PCR analysis revealed that all of the samples from patients with benign diseases presented a predominant expression of the CD44v10 transcript, whereas 26 of the 40 samples from patients with UUT-TCC dominantly expressed the CD44v8-10 transcript. In addition, the positive rate obtained by the CC-RT-PCR analysis was significantly higher than that obtained by cytologic examination, especially in patients with low-grade UUT-TCC. These findings strongly suggest that CC-RT-PCR is a useful noninvasive tool for the diagnosis of UUT-TCC.
Mol Urol 1999
PMID:Utility of Competitive Reverse Transcription-Polymerase Chain Reaction Analysis of Specific CD44 Variant RNA for Detecting Upper Urinary Tract Transitional-Cell Carcinoma. 1085 Dec 97

Down Syndrome (DS) caused by trisomy 21 is the most common birth defect associated with mental retardation. Recently, a novel gene named, DSCAM, has been identified in the DS critical region. DSCAM is predicted to be a transmembrane protein with a very high structural and sequence homology to Ig superfamily of cell adhesion molecules and is expressed in the developing nervous system with the highest level in fetal brain. Diverse glycoproteins of cell surfaces and extracellular matrices operationally termed as 'adhesion molecule' are important in the specification of cell interactions during development, maintenance and regeneration of the nervous system. To understand the cellular function of DSCAM protein, we transfected human DSCAM cDNA into mouse fibroblast L cells and analysed its expression. On Western blot analysis, antibodies raised against recombinant DSCAM-Ig3 recognized a 198 kDa protein band in the membrane fraction of DSCAM transfected L cells. Stable transformants expressing DSCAM showed uniform surface expression. DSCAM-expressing transfectants exhibited enhanced adhesive properties, aggregating with faster kinetics and forming aggregates in a homophilic manner. Divalent cations are not required for this cell aggregation. These results demonstrate that DSCAM is a cell adhesion molecule that can mediate cation-independent homophilic binding activity between DSCAM expressing cells.
Brain Res Mol Brain Res 2000 Jun 23
PMID:Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion. 1092 49

Previous studies have shown that the expression of the cell-cell adhesion molecule (C-CAM1), located at chromosome 19, is down-regulated in several types of human cancers, including prostate and breast cancers. Two major isoforms of C-CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, are derived from the C-CAM1 gene through alternative splicing. Tumor cells transfected with L-form C-CAM1, which contains a cytoplasmic domain, display significantly lower growth rates and less tumorigenicity in both in vitro and in vivo models compared with untransfected tumor cells, suggesting that L-form C-CAM1 may be a tumor suppressor. The transfection of the cytoplasmic domain of L-form C-CAM1 could also cause suppression of tumor growth, further supporting the role of L-form C-CAM1 in tumorigenesis. In contrast to reports of most of the tumor types tested, Ohwada et al. (Am. J. Respir. Cell Mol. Biol., 11: 214-220, 1994) reported that C-CAM1 was not down-regulated or even up-regulated in lung cancer. Because the cytoplasmic domain of L-form C-CAM1 is critical for the tumor suppressor function of C-CAM1, we hypothesized that switching of the isoform rather than down- regulation of C-CAM1 gene expression occurs during lung tumorigenesis. To test this hypothesis, we analyzed pairs of tumor tissue and corresponding normal-appearing lung tissue from 51 patients with non-small cell lung cancer (NSCLC) and 43 cell lines to determine expression profiles of L-form C-CAM1 and S-form C-CAM1 using reverse transcription-PCR. We found that L-form C-CAM1 was the predominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most (84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantly S-form C-CAM1 (P < 0.0001). Similarly, 19 (79%) of the 24 NSCLC cell lines and 17 (85%) of the 20 small cell lung cancer cell lines expressed predominantly S-form C-CAM1. The frequent alteration of the C-CAM1 expression pattern suggests that C-CAM1 has an important role in lung tumorigenesis.
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PMID:C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary lung cancers. 1095 75

T helper type 1 (Th1) cells are important effectors in a number of immune-mediated lung diseases. We recently described a murine model of lung injury induced by adoptive transfer of cloned alloreactive Th1 cells. To investigate mechanisms that result in injury to the lung, we studied the in vivo distribution of (51)Cr-labeled Th1 cells. One hour after intravenous administration, >85% of injected radioactivity was left in the lung, and at 24 h, 40% of radioactivity was left in the lung. Adherence of Th1 cells in the lung was significantly inhibited by neutralizing antibody to lymphocyte function-associated antigen-1. Th1 cell adherence also was decreased in lungs of mice deficient in intercellular adhesion molecule-1 (ICAM-1). Th1 cell transfer further induced expression of ICAM-1 and vascular cell adhesion molecule-1 in the lung. Vascular cell adhesion molecule-1-immunoreactive protein was markedly induced in lung endothelium by alloreactive Th1 cells. These findings indicate that Th1 cells localize in normal lung by a mechanism involving lymphocyte function-associated antigen-1 and ICAM-1. Alloreactive cells further induce endothelial adhesion molecules that may facilitate recruitment of inflammatory cells to the lung and amplify Th1 cell-induced lung injury.
Am J Physiol Lung Cell Mol Physiol 2000 Sep
PMID:Adherence of adoptively transferred alloreactive Th1 cells in lung: partial dependence on LFA-1 and ICAM-1. 1095 34

Neurotrophins (NTs) and their receptors play an essential role in the differentiation and survival of defined neuronal populations of the central and peripheral nervous systems. Their actions, however, do not appear to be limited to the nervous system, as both NTs and their receptors have been found in non neuronal cells, including cells of the endocrine system. At least four of the five known neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and their receptors (p75 NTR, trkA, trkB and trkC) are present in the developing ovary. Using mice carrying null mutations of the genes encoding neurotrophins (NGF, NT-4, BDNF) or the receptor that mediates the actions of NT-4 and BDNF (trkB), we have obtained initial results consistent with the notion that neurotrophins are required for the growth of primordial follicles. NGF-deficient mice show a decreased formation of both primary and secondary preantral follicles. Null mutation of the NT-4 gene failed to affect either folliculogenesis or follicular development. However, formation of primary and secondary follicles was compromised in mice carrying a null mutation of both the NT-4 and BDNF genes, suggesting compensation of function by BDNF in NT-4 knockouts. Support for this concept is provided by the similar deficiency in follicular growth observed in animals carrying a null mutation of the gene encoding trkB, the receptors mediating NT-4 and BDNF actions. Initial experiments, using differential display, to isolate genes that may be involved in the process of folliculogenesis and/or early follicular development, resulted in the isolation of a recently identified cell adhesion molecule and a novel transcription factor originally shown to induce cell transformation. It thus appears that formation and development of mammalian follicles requires the concerted action of genes originally thought to be only involved in cell differentiation/survival of neuronal cells, and genes that may control the growth, differentiation, and cell-cell interactions of somatic and germ cells in the ovary.
Mol Cell Endocrinol 2000 May 25
PMID:Neurotrophic and cell-cell dependent control of early follicular development. 1096 76


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