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Inhibition of protein kinase C results in a switch from a non-motile to a motile phenotype in diverse human lymphocyte populations.
- Source :
- Immunology; Feb95, Vol. 84 Issue 2, p326-332, 7p
- Publication Year :
- 1995
-
Abstract
- Circulating lymphocytes are rounded, non-motile cells which on contact with cytokines, specialized or activated endothelium, acquire a constantly shape-changing, polarized morphology which enables migration into appropriate sites. The biochemical mechanisms which regulate this switch are not understood but the various stimuli may have a common final pathway. In this study we show that protein kinase C (PKC) inhibitors of the bisindolylmaleimide type (GF 109203X, Ro 31-8220, CGP 41 251) induce resting, spherical lymphocytes to change rapidly (<30 min) into polarized, locomotory cells. This phenomenon was seen with diverse populations of blood T lymphocytes, tonsillar B cells and Jurkat and Molt4 T-cell lines. Consistent with this, down- regulation of PKC by chronic treatment (44 hr) with bryostatin also induced the polarized phenotype in blood lymphocytes and non-motile Molt4 cells. Conversely, treatment of a spontaneously motile subline of Molt4 cells with various PKC activators caused a reversion to the non-motile phenotype within minutes. PKC activation must be sufficient to overcome the effects of a constitutively active phosphatase because bisindolylmaleimide induction of motility could be prevented by pretreatment of the cells with a phosphatase inhibitor, calyculin A. It is concluded that, in resting lymphocytes, chronic activation of a PKC offsets the action of a constitutively active phosphatase and the net result is maintenance of the non-motile state. Agents which alter the kinase/phosphatase balance in favour of dephosphorylation result in induction of the locomotory phenotype. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 84
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 13520073