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Your search keyword '"Dougherty, S. T."' showing total 4 results
Start Over Author "Dougherty, S. T." Topic alternative splicing
4 results on '"Dougherty, S. T."'

1. Alternatively spliced CD44 isoforms containing exon v10 promote cellular adhesion through the recognition of chondroitin sulfate-modified CD44.

Author

Chiu RK, Droll A, Dougherty ST, Carpenito C, Cooper DL, and Dougherty GJ

Subjects
Adjuvants, Immunologic, Animals, COS Cells, Cell Adhesion, Cell Line, Transformed, DNA, Complementary, Hyaluronic Acid metabolism, Protein Isoforms, Alternative Splicing, Chondroitin Sulfates metabolism, Exons, Hyaluronan Receptors genetics, Hyaluronan Receptors metabolism
Abstract

Correlations have been noted between the expression of certain alternatively spliced CD44 isoforms and the metastatic propensity of various histologically distinct tumor cell types. The precise mechanism by which particular CD44 isoforms contribute to the metastatic process is, however, unclear. In the present study we demonstrate that CD44R2, a CD44 isoform highly expressed on activated and transformed hemopoietic cells, can recognize and bind a common determinant present on CD44H and CD44R1. Importantly, CD44H lacked this activity. Pretreatment of TIL1 cells expressing CD44H or CD44R1 with chondroitinase ABC inhibited adhesion to CD44R2, suggesting that the unique inserted region present within the CD44R2 molecule, encoded by exon v10, mediates cell adhesion by potentiating the recognition of chondroitin sulfate moieties presented in association with other CD44 molecules. These data help explain the differential involvement of v10-containing CD44 isoforms in tumor metastasis., (Copyright 1999 Academic Press.)

Published
1999
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2. Adhesive interactions between alternatively spliced CD44 isoforms.

Author

Droll A, Dougherty ST, Chiu RK, Dirks JF, McBride WH, Cooper DL, and Dougherty GJ

Subjects
Animals, Antibodies, Monoclonal pharmacology, Blotting, Western, Carrier Proteins genetics, Carrier Proteins metabolism, Cell Aggregation, Cell Line, Chlorocebus aethiops, Epithelium physiology, Fibrosarcoma, Flow Cytometry, Gene Expression, Humans, Hyaluronan Receptors, Leukemia, Erythroblastic, Acute, Lymphoma, Mice, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Receptors, Lymphocyte Homing genetics, Receptors, Lymphocyte Homing metabolism, Recombinant Proteins biosynthesis, Recombinant Proteins metabolism, Transfection, Tumor Cells, Cultured, Alternative Splicing, Carrier Proteins biosynthesis, Cell Adhesion, Receptors, Cell Surface biosynthesis, Receptors, Lymphocyte Homing biosynthesis
Abstract

Alternative splicing of a series of 10 contiguous exons present within the CD44 gene can generate a large number of differentially expressed CD44 isoforms that contain additional peptide sequences of varying length inserted into a single site within the extracellular domain of the molecule proximal to the membrane spanning domain. Although distinct functions have been ascribed to certain of these isoforms, the effect of particular inserted domains on the ligand-binding specificity of the CD44 molecule remains unclear. In the present study, we demonstrate that while CD44H, the major CD44 isoform expressed on resting hemopoietic cells, and CD44R1, an alternatively spliced isoform present on transformed epithelial cells and certain activated and/or malignant hemopoietic cell types, can both bind avidly to hyaluronan, only CD44R1 can promote homotypic cellular aggregation when expressed in the CD44-negative murine lymphoma cell line TIL1. Experiments in which TIL1 cells transduced with different CD44 isoforms were tested for their ability to adhere to one another or to COS7 cells transfected with CD44R1, indicated that CD44R1 can recognize and bind a common determinant present on both CD44H and CD44R1. Monoclonal antibody blocking studies suggest further, that the determinant recognized by CD44R1 is located in a region of the CD44 molecule distinct from that involved in hyaluronan binding.

Published
1995
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3. Molecular mechanisms regulating the hyaluronan binding activity of the adhesion protein CD44

Author

Chiu, R K, Droll, A, Cooper, D L, Dougherty, S T, Dirks, J F, Dougherty, G J, and Department of Sciences

Subjects
DNA, Complementary, Interleukins, Macrophages, T-Lymphocytes, Research Support, Non-U.S. Gov't, Fibroblasts, Flow Cytometry, Hematopoietic Stem Cells, Transfection, Recombinant Proteins, Cell Line, Alternative Splicing, Mice, Hyaluronan Receptors, Mutation, Journal Article, Animals, Humans, Severe Combined Immunodeficiency, Mast Cells, Cloning, Molecular, Hyaluronic Acid, Signal Transduction
Abstract

In the present study, we describe the isolation and characterization of a cDNA clone designated B6F1.3, that appears to 'activate' the hyaluronan-binding capacity of CD44 upon transfection into the murine fibroblastoid cell line MOP8. Sequence analysis indicates that the putative regulatory molecule encoded by this clone is identical to the murine interleukin-2 receptor gamma chain (mIL-2R gamma), a recently described type 1 transmembrane protein that constitutes an integral component of the cell surface receptors that bind a number of cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and perhaps also IL-13. Mutations in this molecule have been shown to be responsible for X-linked severe combined immunodeficiency (XSCID) in humans. With the exception of bone marrow, the mIL-2R gamma chain was found to be expressed at high levels on all hemopoietic cell lines and tissue types examined. Non-hemopoietic tissues are generally negative. FACS analysis and Western blot analysis indicated respectively that B6F1.3 does not mediate its effects by upregulating the expression of CD44 or by altering the alternative splicing of the molecule. Removal of the cytoplasmic tail of the mIL-2R gamma chain, including a Src homology region 2 (SH2) subdomain, abolished its ability to enhance CD44-mediated binding to hyaluronan suggesting the involvement of signal transduction events triggered via the cytoplasmic domain in the 'activation' process. Determining whether activating molecules such as B6F1.3 are co-expressed within tumor cells may help improve the potential value of CD44 as a diagnostic marker of metastatic disease.

Published
1995

4. Adhesive interactions between alternatively spliced CD44 isoforms

Author

Droll, A, Dougherty, S T, Chiu, R K, Dirks, J F, McBride, W H, Cooper, D L, Dougherty, G J, and Department of Sciences

Subjects
Lymphoma, Fibrosarcoma, Research Support, Non-U.S. Gov't, Blotting, Western, Receptors, Lymphocyte Homing, Antibodies, Monoclonal, Gene Expression, Receptors, Cell Surface, Flow Cytometry, Transfection, Epithelium, Recombinant Proteins, Cell Line, Cercopithecus aethiops, Alternative Splicing, Mice, Hyaluronan Receptors, Cell Adhesion, Tumor Cells, Cultured, Journal Article, Animals, Humans, Leukemia, Erythroblastic, Acute, Carrier Proteins, Cell Aggregation
Abstract

Alternative splicing of a series of 10 contiguous exons present within the CD44 gene can generate a large number of differentially expressed CD44 isoforms that contain additional peptide sequences of varying length inserted into a single site within the extracellular domain of the molecule proximal to the membrane spanning domain. Although distinct functions have been ascribed to certain of these isoforms, the effect of particular inserted domains on the ligand-binding specificity of the CD44 molecule remains unclear. In the present study, we demonstrate that while CD44H, the major CD44 isoform expressed on resting hemopoietic cells, and CD44R1, an alternatively spliced isoform present on transformed epithelial cells and certain activated and/or malignant hemopoietic cell types, can both bind avidly to hyaluronan, only CD44R1 can promote homotypic cellular aggregation when expressed in the CD44-negative murine lymphoma cell line TIL1. Experiments in which TIL1 cells transduced with different CD44 isoforms were tested for their ability to adhere to one another or to COS7 cells transfected with CD44R1, indicated that CD44R1 can recognize and bind a common determinant present on both CD44H and CD44R1. Monoclonal antibody blocking studies suggest further, that the determinant recognized by CD44R1 is located in a region of the CD44 molecule distinct from that involved in hyaluronan binding.

Published
1995

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