pubmed-article:20802526 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:20802526 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
pubmed-article:20802526 | lifeskim:mentions | umls-concept:C0006772 | lld:lifeskim |
pubmed-article:20802526 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
pubmed-article:20802526 | lifeskim:mentions | umls-concept:C0542341 | lld:lifeskim |
pubmed-article:20802526 | pubmed:issue | 44 | lld:pubmed |
pubmed-article:20802526 | pubmed:dateCreated | 2010-11-4 | lld:pubmed |
pubmed-article:20802526 | pubmed:abstractText | Fine tuning of Ras activity is widely known as a mechanism to induce different cellular responses. Recently, we have shown that calmodulin (CaM) binds to K-Ras and that K-Ras phosphorylation inhibits its interaction with CaM. In this study we report that CaM inhibits K-Ras phosphorylation at Ser181 by protein kinase C (PKC) in vivo, and this is a mechanism to modulate K-Ras activity and signaling. Although CaM inhibition increased the activation of endogenous K-Ras, PKC inhibition decreased its activation status. We demonstrate that K-Ras phosphorylation decreased susceptibility to p120GAP activity. Accordingly, we also observed that non-phosphorylable K-Ras mutant exhibits a less sustained activation profile and do not efficiently activate AKT at low growth factor doses compared with wild-type K-Ras. It is interesting that the physiological responses induced by K-Ras are affected by this phosphorylation; when K-Ras cannot be phosphorylated it exhibits a remarkably decreased ability to stimulate proliferation in non-saturated serum conditions. Finally, we demonstrate that phosphorylation also regulates oncogenic K-Ras functions, as focus formation capacity, mobility and apoptosis resistance upon adriamycin treatment of cells expressing oncogenic K-Ras that cannot be phosphorylated are highly compromised. Moreover, at low serum concentration proliferation and survival is practically inhibited when cells cannot phosphorylate oncogenic K-Ras. In this condition, K-Ras phosphorylation is essential to ensure a proper activation of mitogen-activated protein kinase and PI3K/AKT pathways. In summary, our findings suggest that the interplay between CaM interaction and PKC phosphorylation is essential to regulate non-oncogenic and oncogenic K-Ras activity and functionality. | lld:pubmed |
pubmed-article:20802526 | pubmed:language | eng | lld:pubmed |
pubmed-article:20802526 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:20802526 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20802526 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:20802526 | pubmed:month | Nov | lld:pubmed |
pubmed-article:20802526 | pubmed:issn | 1476-5594 | lld:pubmed |
pubmed-article:20802526 | pubmed:author | pubmed-author:BachsOO | lld:pubmed |
pubmed-article:20802526 | pubmed:author | pubmed-author:AgellNN | lld:pubmed |
pubmed-article:20802526 | pubmed:author | pubmed-author:López-AlcaláC... | lld:pubmed |
pubmed-article:20802526 | pubmed:author | pubmed-author:DrostenMM | lld:pubmed |
pubmed-article:20802526 | pubmed:author | pubmed-author:Alvarez-MoyaB... | lld:pubmed |
pubmed-article:20802526 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:20802526 | pubmed:day | 4 | lld:pubmed |
pubmed-article:20802526 | pubmed:volume | 29 | lld:pubmed |
pubmed-article:20802526 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:20802526 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:20802526 | pubmed:pagination | 5911-22 | lld:pubmed |
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pubmed-article:20802526 | pubmed:year | 2010 | lld:pubmed |
pubmed-article:20802526 | pubmed:articleTitle | K-Ras4B phosphorylation at Ser181 is inhibited by calmodulin and modulates K-Ras activity and function. | lld:pubmed |
pubmed-article:20802526 | pubmed:affiliation | Departament de Biologia Cel.lular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain. | lld:pubmed |
pubmed-article:20802526 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:20802526 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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