1.CD98 activation increases surface expression and clusteringof beta 1 integrins in MCF-7 cells through FAK/Src- and cytoskeleton-independent mechanisms.
Experimental & Molecular Medicine 2008;40(3):261-270
CD98, a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein, regulates beta 1 integrin- mediated cell adhesion. However, the molecular mechanisms underlying CD98-mediated activation of beta 1 integrin are presently unclear. In this study, the effects of CD98 signaling on the expression and clustering of beta 1 integrin were investigated. Activation of CD98 augmented surface expression of beta 1 integrin on MCF-7 cells. Cross-linking CD98 induced clustering of beta 1 integrins. Inhibition of phosphorylation of focal adhesion kimase (FAK) by PP2, an inhibitor of Src family kinase, reduced cell-extracellular matrix adhesion, but not surface expression and clustering of beta1 integrin on MCF-7 cells. This result was confirmed by over-expression of dominant negative forms of FAK. In addition, phalloidin or cytochalasin D inhibited CD98-mediated induction of cell-ECM adhesion, but not surface expression and clustering of b1 integrins. The inhibitory effects of PP2, cytochalasin D or phalloidin on CD98-stimulated cell adhesion were diminished by pretreatment of cells with Mn2+, which is shown to induce conformational change of integrins. These results provide the first evidence that CD98 activation increases not only beta1 integrin affinity but also its surface expression and clustering and the latter is independent of FAK/Src and cytoskeleton.
Antigens, CD29/*biosynthesis/genetics
;
Antigens, CD98/agonists/*metabolism
;
Cell Line, Tumor
;
Cytochalasin D/pharmacology
;
Cytoskeleton/drug effects/enzymology
;
Focal Adhesion Kinase 2/genetics/*metabolism
;
Focal Adhesions/drug effects/enzymology
;
Humans
;
Microscopy, Confocal
;
Multiprotein Complexes/*biosynthesis/genetics
;
Mutant Proteins/genetics/metabolism
;
Phalloidine/pharmacology
;
Phosphorylation/drug effects
;
Protein Binding
;
Pyrimidines/pharmacology
;
Signal Transduction/physiology
;
Transfection
2.Induction of Upregulation and Downregulation of the T-Cell Activation Marker CD98 in Patients Undergoing Contrast-Enhanced CT with Iodinated Non-Ionic Dimeric Contrast Medium.
Korean Journal of Radiology 2009;10(1):58-62
OBJECTIVE: This study was designed to determine prospectively the expression of the multifunctional CD98 protein in peripheral white blood cells in patients receiving iodinated contrast media (CM) for a computed tomography (CT) examination. MATERIALS AND METHODS: In 12 adult patients that received non-ionic dimeric CM (iosimenol or iodixanol), the expression of CD98 was analyzed from samples of peripheral white blood cells obtained prior to, one hour, and 24 hours after CM injection by the use of flow cytometry analysis and the use of the direct immunofluorescence technique. RESULTS: Overall, expression of CD98 was significantly downregulated 24 hours after CM injection (51.9% +/- 10.8% vs. 38.8% +/- 16.9%; p < 0.04). Patients that received iosimenol exhibited a more pronounced but not significant decrease of CD98 expression both one hour and 24 hours after CM injection. In an analysis of specific patient responses, CD98 downregulation occurred in eight patients. In two patients, CD98 was upregulated, and in the remaining two patients, expression remained unchanged. No patient acquired an adverse CM reaction. CONCLUSION: This is the first demonstration that CM may be a regulator of CD98 expression. To determine if upregulation is associated with an increased risk for the acquisition of an adverse CM-induced hypersensitivity reaction and if downregulation is associated without a risk for the acquisition of an adverse CM-induced hypersensitivity reaction, further studies with a larger population of patients are required.
Adult
;
Antigens, CD98/*metabolism
;
Benzamides/diagnostic use/*pharmacology
;
Contrast Media/*pharmacology
;
Down-Regulation/*drug effects
;
Female
;
Flow Cytometry
;
Humans
;
Lymphocyte Activation
;
Male
;
Middle Aged
;
Propanolamines/diagnostic use/*pharmacology
;
T-Lymphocytes/*drug effects/immunology
;
*Tomography, X-Ray Computed
;
Triiodobenzoic Acids/diagnostic use/*pharmacology
;
Up-Regulation/*drug effects
3.The First Korean Case of Lysinuric Protein Intolerance: Presented with Short Stature and Increased Somnolence.
Jung Min KO ; Choong Ho SHIN ; Sei Won YANG ; Moon Woo SEONG ; Sung Sup PARK ; Junghan SONG
Journal of Korean Medical Science 2012;27(8):961-964
Lysinuric protein intolerance (LPI) is a rare inherited metabolic disease, caused by defective transport of dibasic amino acids. Failure to thrive, hepatosplenomegaly, hematological abnormalities, and hyperammonemic crisis are major clinical features. However, there has been no reported Korean patient with LPI as of yet. We recently encountered a 3.7-yr-old Korean girl with LPI and the diagnosis was confirmed by amino acid analyses and the SLC7A7 gene analysis. Her initial chief complaint was short stature below the 3rd percentile and increased somnolence for several months. Hepatosplenomegaly was noted, as were anemia, leukopenia, elevated levels of ferritin and lactate dehydrogenase, and hyperammonemia. Lysine, arginine, and ornithine levels were low in plasma and high in urine. The patient was a homozygote with a splicing site mutation of IVS4+1G > A in the SLC7A7. With the implementation of a low protein diet, sodium benzoate, citrulline and L-carnitine supplementation, anemia, hyperferritinemia, and hyperammonemia were improved, and normal growth velocity was observed.
Amino Acid Metabolism, Inborn Errors/complications/diet therapy/*genetics
;
Antifungal Agents/therapeutic use
;
Antigens, CD98 Light Chains/genetics
;
Asian Continental Ancestry Group/*genetics
;
Carnitine/therapeutic use
;
Child, Preschool
;
Citrulline/therapeutic use
;
Diet, Protein-Restricted
;
Disorders of Excessive Somnolence/complications/*diagnosis/drug therapy
;
Female
;
Growth Disorders/complications/*diagnosis
;
Homozygote
;
Humans
;
Hypercalcemia/complications/*diagnosis
;
Metabolic Diseases/complications/*diagnosis
;
Mutation
;
Nephrocalcinosis/complications/*diagnosis
;
Republic of Korea
;
Sequence Analysis, DNA
;
Sodium Benzoate/therapeutic use
;
Vitamin B Complex/therapeutic use