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Cell. 2001 Apr 6;105(1):69-79.

Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction.

Author information

1
Department of Cell Biology and Program in Neuroscience, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

Abstract

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.

PMID:
11301003
DOI:
10.1016/s0092-8674(01)00297-5
[Indexed for MEDLINE]
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