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Sci. STKE, 13 November 2001
Vol. 2001, Issue 108, p. tw421
[DOI: 10.1126/stke.2001.108.tw421]


PX Domains Signaling from Endosomes

PX domains are phosphatidylinositol (PI) lipid-binding domains that in some proteins interact specifically with phosphatidylinositol 3-phosphate [PI(3)P]. Cytokine-independent survival kinase (CISK) contains a PX domain that specifically binds PI(3)P, but does not bind other 3-phosphorylated species, such as PI(3,4)P and PI(3,5)P. A CISK-green fluorescent protein (GFP) fusion protein or fusion protein with a mutated and inactive kinase domain localized to endosomes. However, mutation of a conserved tyrosine (Y51A) in the PX domain abolished endosomal localization. Localization to the endosome was required for activation of CISK. Cells expressing CISK stimulated with insulin-like growth factor-1 (IGF-1) or epidermal growth factor (EGF) exhibited enhanced phosphorylation of histone 2B. This increase in kinase activity did not occur in cells expressing CISK Y51A or in cells treated with wortmannin to disrupt the endosomal system. Thus, CISK represents another example of a signaling pathway emanating from the endosomal compartment, which is initiated by changes in phosphatidylinositol lipids.

J. V. Virbasius, X. Song, D. P. Pomerleau, Y. Zhan, G. W. Zhou, M. P. Czech, Activation of the Akt-related cytokine-independent survival kinase requires interaction of its phox domain with endosomal phosphatidylinositol 3-phosphate Proc. Natl. Acad. Sci. U.S.A. 98, 12908-12913 (2001). [Abstract] [Full Text]

Citation: Signaling from Endosomes. Sci. STKE 2001, tw421 (2001).

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