Signal Transduction

Screening for Kinases

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Science  24 Oct 2008:
Vol. 322, Issue 5901, pp. 507
DOI: 10.1126/science.322.5901.507c

Hedgehog (Hh) ligands are regulators of developmental patterning, and overactivity of the Hh signaling pathway is associated with some human cancers. Genetic approaches in Drosophila have identified many components of the signaling pathway, but Hh signaling is still incompletely understood, particularly in vertebrates, in which the components of the pathway differ substantially from their counterparts in flies. Evangelista et al. searched for protein kinases that influenced Hh signaling by monitoring the effects of a library of siRNA molecules on the expression of a reporter gene in mammalian cells. One kinase identified in the screen was a member of the cyclin-dependent kinase family, Cdc2l1, which regulates mitosis and apoptosis; Cdc2l1 directly interacts with Suppressor of Fused (an inhibitor that keeps the Gli transcription factor from moving to the nucleus and activating Hh-dependent gene transcription). Overexpression of Cdc2l1 in cultured cells or in zebrafish embryos enhanced Hh signaling. Thus, the authors propose that Cdc2l1 is a component of the Hh pathway that may have been missed in genetic screens because of the harmful effects of the loss of a multifunctional protein. — LBR

Sci. Signal. 1, ra7 (2008).

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