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Semaphorins Signal a New Pathway

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Science  20 Sep 2002:
Vol. 297, Issue 5589, pp. 1961
DOI: 10.1126/science.297.5589.1961b

The semaphorins, a large family of secreted and membrane-bound proteins, regulate axonal pathfinding and play a prominent role in nervous system development. The widespread distribution of semaphorin receptors, or plexins, in various adult and embryonic tissues, however, suggests that these proteins may serve nonneuronal functions as well.

Giordano et al. found that Semaphorin 4D (Sema 4D) elicited a pattern of cell proliferation, migration, anchorage-independent growth, and branching morphology in a hepatic cell line. The response was identical to “invasive growth,” a programmed cellular response to Scatter Factor 1 due to activation of the Met receptor. Endogenous Plexin B1—the Sema 4D receptor—and Met formed a complex. Sema 4D elicited tyrosine phosphorylation of Plexin B1, Met, and a Met substrate. Cells overexpressing Plexin B1 constitutively displayed the invasive phenotype and showed basal Met phosphorylation. The response to Sema 4D depended on expression of a functional Met receptor and was inhibited by a Met dominant negative construct. This expands the known spectrum of semaphorin functions and raises the intriguing possibility that the semaphorins could be implicated in metastatic processes through activation of the Met pathway. — EA

Nature Cell Biol.4, 720 (2002).

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