期刊
EXPERIMENTAL CELL RESEARCH
卷 313, 期 20, 页码 4170-4179出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2007.07.019
关键词
Eph; ephrin; transglutaminase; oligomerization; clustering
The Eph receptors and their ligands, the ephrins, are thought to act at points of close cell-cell contact to elicit bi-directional signaling in receptor and ligand expressing cells. However, when cultured in vitro, some A-type ephrins are released from the cell surface and it is unclear if these soluble ephrins participate in Eph receptor activation. We show that soluble ephrin A5 is subject to oligomerization. Ephrins A1 and A5 are substrates for a cross-linking enzyme, tissue trans glutaminase, which mediates the formation of oligomeric ephrin. Trans glutaminase-cross-linked ephrin binds to A-type Eph receptors, stimulates Eph kinase activity, and promotes invasion and migration of HeLa cells. Trans glutaminase-mediated oligomerization of soluble ephrin potentially represents a novel mechanism of forward signaling through Eph receptors and may extend the influence of A-type ephrins beyond cell contact mediated signaling. (c) 2007 Elsevier Inc. All rights reserved.
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