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Differential role of tyrosine phosphorylation in adhesion‐induced transcription, mRNA stability, and cytoskeletal organization in human monocytes
Author(s) -
Mondal Krishna,
Sirenko Oksana I.,
Lofquist Alan K.,
Morris John S.,
Haskill J. Stephen,
Watson Joanna M.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.2.216
Subject(s) - tyrosine phosphorylation , biology , microbiology and biotechnology , phosphorylation , protein tyrosine phosphatase , tyrosine kinase , signal transduction
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.