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      RhoH is required to maintain the integrin LFA-1 in a nonadhesive state on lymphocytes.

      Nature immunology

      genetics, immunology, Electrophoresis, Polyacrylamide Gel, Flow Cytometry, Humans, Intercellular Adhesion Molecule-1, metabolism, Jurkat Cells, Lymphocyte Function-Associated Antigen-1, Mutation, RNA, Messenger, analysis, Signal Transduction, T-Lymphocytes, Transcription Factors, rho GTP-Binding Proteins, Blotting, Southern, Cell Adhesion

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          Abstract

          Lymphocyte function-associated antigen 1 (LFA-1) is relatively nonadhesive on resting lymphocytes; however, the mechanisms underlying changes in its adhesiveness are poorly understood. In this study, we generated a Jurkat T cell clone, J+hi1.14, that contained low amounts of mRNA for RhoH, a leukocyte-specific inhibitory Rho family member. J+hi1.14 cells expressed constitutively adhesive LFA-1 and the cells bound spontaneously to intracellular adhesion molecules 1, 2 and 3. Reconstitution of RhoH mRNA expression in J+hi1.14 cells reverted the adhesion phenotype to that of wild-type. We obtained similar results using RNA interference in peripheral blood lymphocytes. These data demonstrate that RhoH is required for maintenance of lymphocyte LFA-1 in a nonadhesive state.

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          Most cited references 41

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          Detection of specific sequences among DNA fragments separated by gel electrophoresis

           E.M. Southern (1975)
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            Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes.

            By analyzing the effects of single base substitutions around the ATG initiator codon in a cloned preproinsulin gene, I have identified ACCATGG as the optimal sequence for initiation by eukaryotic ribosomes. Mutations within that sequence modulate the yield of proinsulin over a 20-fold range. A purine in position -3 (i.e., 3 nucleotides upstream from the ATG codon) has a dominant effect; when a pyrimidine replaces the purine in position -3, translation becomes more sensitive to changes in positions -1, -2, and +4. Single base substitutions around an upstream, out-of-frame ATG codon affect the efficiency with which it acts as a barrier to initiating at the downstream start site for preproinsulin. The optimal sequence for initiation defined by mutagenesis is identical to the consensus sequence that emerged previously from surveys of translational start sites in eukaryotic mRNAs. The mechanism by which nucleotides flanking the ATG codon might exert their effect is discussed.
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              Adhesion receptors of the immune system.

               T. Springer (1990)
              The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life. Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses.
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                Author and article information

                Journal
                10.1038/ni1103
                15300248

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