An Eph receptor regulates integrin activity through R-Ras

Proceedings of the National Academy of Sciences of the United States of America - Tập 96 Số 24 - Trang 13813-13818 - 1999
June X. Zou1, Binghe Wang1, Matthew S. Kalo1, Andreas H. Zisch1, Elena B. Pasquale1, Erkki Ruoslahti1
1Cancer Research Center, The Burnham Institute, La Jolla, CA 92037

Tóm tắt

The ability of integrins to mediate cell attachment to extracellular matrices and to blood proteins is regulated from inside the cell. Increased ligand-binding activity of integrins is critical for platelet aggregation upon blood clotting and for leukocyte extravasation to inflamed tissues. Decreased adhesion is thought to promote tumor cell invasion. R-Ras, a small intracellular GTPase, regulates the binding of integrins to their ligands outside the cell. Here we show that the Eph receptor tyrosine kinase, EphB2, can control integrin activity through R-Ras. Cells in which EphB2 is activated become poorly adherent to substrates coated with integrin ligands, and a tyrosine residue in the R-Ras effector domain is phosphorylated. The R-Ras phosphorylation and loss of cell adhesion are causally related, because forced expression of an R-Ras variant resistant to phosphorylation at the critical site made cells unresponsive to the anti-adhesive effect of EphB2. This is an unusual regulatory pathway among the small GTPases. Reduced adhesiveness induced through the Eph/R-Ras pathway may explain the repulsive effect of the Eph receptors in axonal pathfinding and may facilitate tumor cell invasion and angiogenesis.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 96 Số 24

13813-13818

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