Editors' ChoiceRas signaling

Ras signaling: Two Effector Pathways May Share CNK

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Science's STKE  16 Nov 1999:
Vol. 1999, Issue 8, pp. tw3
DOI: 10.1126/stke.1999.8.tw3

The small GTP-binding protein Ras relays signals from the cell surface to numerous downstream effector pathways, one of which includes the protein kinase Raf and MAP kinase. Kinase suppressor of Ras (KSR) and connector enhancer of KSR (CNK) are known regulators the the Raf-MAP kinase pathway in the developing Drosophila eye. Although CNK enhances Ras signaling in this system, it also suppresses Raf activity. Therrien et al. show that these two regulatory effects map to opposite ends of the CNK protein. By overexpressing truncated forms of CNK in the developing Drosophila eye, the authors determined that the ability of CNK to repress Raf activity localized to its COOH-terminus, a region known to bind Raf. The ability of CNK to enhance Ras signaling in this system resided in the NH2-terminus of CNK. The NH2-terminus had no effect on MAP kinase activity in cultured cells, and CNK appeared to activate the MAP kinase-independent effector pathway of Ras that involves the protein RAL. The authors propose that CNK may function in more than one pathway downstream of Ras.

Therrien, M., Wong, A.M., Kwan, E., and Rubin, G.M. (1999) Functional analysis of CNK in RAS signaling. Proc. Natl. Acad. Sci. U.S.A. 96: 13259-13263. [Abstract] [Full Text]

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