| Title |
Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB
|
|---|---|
| Published in |
Proceedings of the National Academy of Sciences of the United States of America, January 2011
|
| DOI | 10.1073/pnas.1017831108 |
| Pubmed ID | |
| Authors |
David Maag, Micah J. Maxwell, Douglas A. Hardesty, Katie L. Boucher, Namrata Choudhari, Adam G. Hanno, Jenny F., Adele S. Snowman, Joseph W. Pietropaoli, Risheng Xu, Phillip B. Storm, Adolfo Saiardi, Solomon H. Snyder, Adam C. Resnick |
| Abstract |
The second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP(3)), formed by the p110 family of PI3-kinases, promotes cellular growth, proliferation, and survival, in large part by activating the protein kinase Akt/PKB. We show that inositol polyphosphate multikinase (IPMK) physiologically generates PIP(3) as well as water soluble inositol phosphates. IPMK deletion reduces growth factor-elicited Akt signaling and cell proliferation caused uniquely by loss of its PI3-kinase activity. Inhibition of p110 PI3-kinases by wortmannin prevents IPMK phosphorylation and activation. Thus, growth factor stimulation of Akt signaling involves PIP(3) generation through the sequential activations of the p110 PI3-kinases and IPMK. As inositol phosphates inhibit Akt signaling, IPMK appears to act as a molecular switch, inhibiting or stimulating Akt via its inositol phosphate kinase or PI3-kinase activities, respectively. Drugs regulating IPMK may have therapeutic relevance in influencing cell proliferation. |
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Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 3% |
| Portugal | 1 | <1% |
| Japan | 1 | <1% |
| United Kingdom | 1 | <1% |
| Finland | 1 | <1% |
| Czechia | 1 | <1% |
| Belgium | 1 | <1% |
| Unknown | 99 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 32 | 30% |
| Researcher | 19 | 18% |
| Professor > Associate Professor | 9 | 8% |
| Student > Bachelor | 8 | 7% |
| Student > Doctoral Student | 7 | 6% |
| Other | 15 | 14% |
| Unknown | 18 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 39 | 36% |
| Biochemistry, Genetics and Molecular Biology | 26 | 24% |
| Medicine and Dentistry | 8 | 7% |
| Chemistry | 7 | 6% |
| Engineering | 4 | 4% |
| Other | 5 | 5% |
| Unknown | 19 | 18% |