The Tyrosine Kinase p56lck Mediates Activation of Swelling-induced Chloride Channels in Lymphocytes
Open Access
- 6 April 1998
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 141 (1) , 281-286
- https://doi.org/10.1083/jcb.141.1.281
Abstract
Osmotic cell swelling activates Cl− channels to achieve anion efflux. In this study, we find that both the tyrosine kinase inhibitor herbimycin A and genetic knockout of p56lck, a src-like tyrosine kinase, block regulatory volume decrease (RVD) in a human T cell line. Activation of a swelling-activated chloride current (ICl−swell) by osmotic swelling in whole-cell patch-clamp experiments is blocked by herbimycin A and lavendustin. Osmotic activation of ICl−swell is defective in p56lck-deficient cells. Retransfection of p56lck restores osmotic current activation. Furthermore, tyrosine kinase activity is sufficient for activation of ICl−swell. Addition of purified p56lck to excised patches activates an outwardly rectifying chloride channel with 31 pS unitary conductance. Purified p56lck washed into the cytoplasm activates ICl−swell in native and p56lck-deficient cells even when hypotonic intracellular solutions lead to cell shrinkage. When whole-cell currents are activated either by swelling or by p56lck, slow single-channel gating events can be observed revealing a unitary conductance of 25–28 pS. In accordance with our patch-clamp data, osmotic swelling increases activity of immunoprecipitated p56lck. We conclude that osmotic swelling activates ICl−swell in lymphocytes via the tyrosine kinase p56lck.Keywords
This publication has 30 references indexed in Scilit:
- Regulation of a swelling‐activated chloride current in bovine endothelium by protein tyrosine phosphorylation and G proteinsThe Journal of Physiology, 1998
- Cell swelling activates ATP-dependent voltage-gated chloride channels in M-1 mouse cortical collecting duct cells.The Journal of general physiology, 1996
- Activation of extracellular signal‐regulated protein kinase (ERK/MAP kinase) following CD28 cross‐linking: activation in cells lacking p56lckTissue Antigens, 1995
- Ca2+ influx pathways mediated by swelling or stores depletion in mouse thymocytes.The Journal of general physiology, 1995
- CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATPCell, 1995
- Single-channel properties of a volume-sensitive anion conductance. Current activation occurs by abrupt switching of closed channels to an open state.The Journal of general physiology, 1995
- Chloride channels activated by osmotic stress in T lymphocytes.The Journal of general physiology, 1993
- CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationshipNature, 1993
- Regulation of CI− channels by multifunctional CaM kinaseNeuron, 1991
- Cell Volume Regulation in LymphocytesKidney and Blood Pressure Research, 1988