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Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides
PKB/Akt and serum and glucocorticoid–regulated kinase (SGK) family kinases are important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have been shown to mediate a variety of cellular processes, including cell growth and survival. Although regulation of Akt can be achieved through s...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196448/ https://www.ncbi.nlm.nih.gov/pubmed/11514587 http://dx.doi.org/10.1083/jcb.200105089 |
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author | Xu, Jun Liu, Dan Gill, Gordon Songyang, Zhou |
author_facet | Xu, Jun Liu, Dan Gill, Gordon Songyang, Zhou |
author_sort | Xu, Jun |
collection | PubMed |
description | PKB/Akt and serum and glucocorticoid–regulated kinase (SGK) family kinases are important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have been shown to mediate a variety of cellular processes, including cell growth and survival. Although regulation of Akt can be achieved through several mechanisms, including its phosphoinositide-binding Pleckstrin homology (PH) domain, how SGK kinases are targeted and regulated remains to be elucidated. Unlike Akt, cytokine-independent survival kinase (CISK)/SGK3 contains a Phox homology (PX) domain. PX domains have been implicated in several cellular events involving membrane trafficking. However, their precise function remains unknown. We demonstrate here that the PX domain of CISK interacts with phosphatidylinositol (PtdIns)(3,5)P(2), PtdIns(3,4,5)P(3), and to a lesser extent PtdIns(4,5)P(2). The CISK PX domain is required for targeting CISK to the endosomal compartment. Mutation in the PX domain that abolished its phospholipid binding ability not only disrupted CISK localization, but also resulted in a decrease in CISK activity in vivo. These results suggest that the PX domain regulates CISK localization and function through its direct interaction with phosphoinositides. Therefore, CISK and Akt have evolved to utilize different lipid binding domains to accomplish a similar mechanism of activation in response to PI-3 kinase signaling. |
format | Text |
id | pubmed-2196448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21964482008-05-01 Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides Xu, Jun Liu, Dan Gill, Gordon Songyang, Zhou J Cell Biol Report PKB/Akt and serum and glucocorticoid–regulated kinase (SGK) family kinases are important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have been shown to mediate a variety of cellular processes, including cell growth and survival. Although regulation of Akt can be achieved through several mechanisms, including its phosphoinositide-binding Pleckstrin homology (PH) domain, how SGK kinases are targeted and regulated remains to be elucidated. Unlike Akt, cytokine-independent survival kinase (CISK)/SGK3 contains a Phox homology (PX) domain. PX domains have been implicated in several cellular events involving membrane trafficking. However, their precise function remains unknown. We demonstrate here that the PX domain of CISK interacts with phosphatidylinositol (PtdIns)(3,5)P(2), PtdIns(3,4,5)P(3), and to a lesser extent PtdIns(4,5)P(2). The CISK PX domain is required for targeting CISK to the endosomal compartment. Mutation in the PX domain that abolished its phospholipid binding ability not only disrupted CISK localization, but also resulted in a decrease in CISK activity in vivo. These results suggest that the PX domain regulates CISK localization and function through its direct interaction with phosphoinositides. Therefore, CISK and Akt have evolved to utilize different lipid binding domains to accomplish a similar mechanism of activation in response to PI-3 kinase signaling. The Rockefeller University Press 2001-08-20 /pmc/articles/PMC2196448/ /pubmed/11514587 http://dx.doi.org/10.1083/jcb.200105089 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Report Xu, Jun Liu, Dan Gill, Gordon Songyang, Zhou Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides |
title | Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides |
title_full | Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides |
title_fullStr | Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides |
title_full_unstemmed | Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides |
title_short | Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides |
title_sort | regulation of cytokine-independent survival kinase (cisk) by the phox homology domain and phosphoinositides |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196448/ https://www.ncbi.nlm.nih.gov/pubmed/11514587 http://dx.doi.org/10.1083/jcb.200105089 |
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