Sci. STKE, 11 September 2007
MAPK Pathway Sequestered at the Golgi
Nancy R. Gough
Science's STKE, AAAS, Washington, DC 20005, USA
Feng et al. identified a Golgi-localized protein with seven putative transmembrane domains as an interacting partner for Raf-1. This protein, which was previously cloned and named PAQR3, they renamed as Raf kinase trapping to Golgi (RKTG). In overexpression assays, RKTG inhibited growth factor-induced signaling and responses in HEK293T (human embryonic kidney) cells and PC12 cells (a pheochromocytoma cell line). RKTG did not inhibit the mitogen-activated protein kinase (MAPK) pathway if a plasma membrane-targeted mutant of Raf-1 was coexpressed or if the pathway was directly activated at the level of the MAPK kinase MEK. Transfected cells exhibited colocalization of RKTG and Raf-1 at the Golgi, and endogenous RKTG and Raf-1 from HEK293T cells coimmunoprecipitated. When overexpressed, RKTG decreased the interaction between tagged Raf-1 and its downstream target MEK and its upstream activator Ras. In RKTG knockout mice, the basal phosphorylation of the MAPK ERK was increased in brain and liver. Mouse embryo fibroblasts from the knockout mice exhibited enhanced ERK phosphorylation (both the amount and duration) in response to growth factor stimulation. Given that spatial regulation of the MAPK pathway is well known for other components in the pathway, it will be interesting to determine whether RKTG-mediated sequestration of Raf-1 not only inhibits signaling to ERK but also may redirect signaling through a different path to other effectors.
L. Feng, X. Xie, Q. Ding, X. Luo, J. He, F. Fan, W. Liu, Z. Wang, Y. Chen, Spatial regulation of Raf kinase signaling by RKTG. Proc. Natl. Acad. Sci. U.S.A. 104, 14348-14353 (2007). [Abstract] [Full Text]
Citation: N. R. Gough, Sequestered at the Golgi. Sci. STKE 2007, tw324 (2007).
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