TY - JOUR
T1 - Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes
AU - Elliott, James I.
AU - Surprenant, Annamarie
AU - Marelli-Berg, Federica M.
AU - Cooper, Joanne C.
AU - Cassady-Cain, Robin L.
AU - Wooding, Carol
AU - Linton, Kenneth
AU - Alexander, Denis R.
AU - Higgins, Christopher F.
PY - 2005/8
Y1 - 2005/8
N2 - Phosphatidylserine (PS) exposure is normally associated with apoptosis and the removal of dying cells. We observed that PS is exposed constitutively at high levels on T lymphocytes that express low levels of the transmembrane tyrosine phosphatase CD45RB. CD45 was shown to be a negative regulator of PS translocation in response to various signals, including activation of the ATP receptor P2X 7. Changes in PS distribution were shown to modulate several membrane activities: Ca 2+ and Na + uptake through the P2X 7 cation channel itself; P2X 7-stimulated shedding of the homing receptor CD62L; and reversal of activity of the multidrug transporter P-glycoprotein. The data identify a role for PS distribution changes in signal transduction, rapidly modulating the activities of several membrane proteins. This seems to be an all-or-none effect, coordinating the activity of most or all the molecules of a target protein in each cell. The data also suggest a new approach to circumventing multidrug resistance.
AB - Phosphatidylserine (PS) exposure is normally associated with apoptosis and the removal of dying cells. We observed that PS is exposed constitutively at high levels on T lymphocytes that express low levels of the transmembrane tyrosine phosphatase CD45RB. CD45 was shown to be a negative regulator of PS translocation in response to various signals, including activation of the ATP receptor P2X 7. Changes in PS distribution were shown to modulate several membrane activities: Ca 2+ and Na + uptake through the P2X 7 cation channel itself; P2X 7-stimulated shedding of the homing receptor CD62L; and reversal of activity of the multidrug transporter P-glycoprotein. The data identify a role for PS distribution changes in signal transduction, rapidly modulating the activities of several membrane proteins. This seems to be an all-or-none effect, coordinating the activity of most or all the molecules of a target protein in each cell. The data also suggest a new approach to circumventing multidrug resistance.
UR - https://www.scopus.com/pages/publications/23144448574
U2 - 10.1038/ncb1279
DO - 10.1038/ncb1279
M3 - Article
C2 - 16025105
SN - 1465-7392
VL - 7
SP - 808
EP - 816
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 8
ER -