Differential role of tyrosine phosphorylation in adhesion-induced transcription, mRNA stability, and cytoskeletal organization in human monocytes
| Autor: | J. S. Haskill, Joanna M. Watson, John S. Morris, Krishna Mondal, A K Lofquist, O I Sirenko |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Transcription Genetic MAP Kinase Signaling System p38 mitogen-activated protein kinases Recombinant Fusion Proteins Immunology Protein tyrosine phosphatase chemistry.chemical_compound Cell Adhesion Immunology and Allergy Humans Protein phosphorylation RNA Messenger Enzyme Inhibitors Phosphorylation Transcription factor Cytoskeleton Cell Size biology NF-kappa B Tyrosine phosphorylation Cell Biology Protein-Tyrosine Kinases Molecular biology Genistein Cell biology Transcription Factor AP-1 chemistry Gene Expression Regulation Mitogen-activated protein kinase biology.protein Leukocytes Mononuclear Cytokines Signal transduction Protein Tyrosine Phosphatases Protein Processing Post-Translational Signal Transduction |
| Zdroj: | Journal of leukocyte biology. 67(2) |
| ISSN: | 0741-5400 |
| Popis: | Monocyte adhesion resulted in rapid tyrosine phosphorylation and subsequent cytokine mRNA induction. The objective of this study was to determine the role of specific tyrosine phosphorylation events, particularly those involving members of the MAP kinase family, in regulating adhesion-induced cytokine expression. Using nuclear run-on analyses, we demonstrated that on adhesion, monocytes rapidly transcriptionally activated numerous cytokine mRNAs, coincident with the activation of the transcription factors NF-κB and AP-1. Both an inhibitor of tyrosine phosphorylation, genistein, and the cytoplasmic tyrosine phosphatase PTP1B, were unable to prevent adhesion-mediated transcriptional activation. However, both blocked adhesion-induced ERK and JNK but not p38 kinase activation and at the same time decreased the stability of interleukin-1β (IL-1β) and IL-8 transcripts. In addition, whereas adhesive events occurred in the presence of genistein and PTP1B, monocyte spreading was markedly inhibited. Our results suggest that the majority of protein phosphorylation events are associated with adhesion-induced cytokine expression through transcript stabilization and cytoskeletal organization. A minority of protein phosphorylation events, not sensitive to genistein or PTP1B exposure, may be instrumental in regulating transcription. Thus the spectrum of protein tyrosine kinases required for transcription appear distinct from those involved in maintaining the stability of some cytokine mRNAs and the integrity of the cytoskeleton to which mRNA destined for translation must be associated. J. Leukoc. Biol. 67: 216–225; 2000. |
| Databáze: | OpenAIRE |
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