TY - JOUR
T1 - Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction
AU - Lu, Qiang
AU - Sun, Edna E.
AU - Klein, Robyn S.
AU - Flanagan, John G.
N1 - Funding Information:
We thank Marc Kirschner, Andrew Luster, Gabriel Corfas, Rosalind Segal, David Van Vactor, Kristen Kwan, Robert Davis, David Feldheim, Michael Hansen, Massimo D'Apuzzo, Gentry Patrick, Adrian Salic, Ethan Lee, Nancy Kaufman, Jack Bateman, David Wilkinson, Georg Mellitzer, Stanley Hollenberg, Gen Suzuki, Morgan Sheng, Dan Pak, Dennis Ausiello, and David Clapham for help, advice, and discussions. This work was supported by a Klingenstein fellowship to J. G. F. and NIH grants HD29417 and NS40043.
PY - 2001/4/6
Y1 - 2001/4/6
N2 - Transmembrane B ephrins and their Eph receptors signal bidirectionally. However, neither the cell biological effects nor signal transduction mechanisms of the reverse signal are well understood. We describe a cytoplasmic protein, PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 can mediate signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein-coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. This study reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues.
AB - Transmembrane B ephrins and their Eph receptors signal bidirectionally. However, neither the cell biological effects nor signal transduction mechanisms of the reverse signal are well understood. We describe a cytoplasmic protein, PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 can mediate signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein-coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. This study reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues.
UR - http://www.scopus.com/inward/record.url?scp=0035815305&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(01)00297-5
DO - 10.1016/S0092-8674(01)00297-5
M3 - Article
C2 - 11301003
AN - SCOPUS:0035815305
SN - 0092-8674
VL - 105
SP - 69
EP - 79
JO - Cell
JF - Cell
IS - 1
ER -