Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals. Export

@article{citeulike:599318, abstract = {BACKGROUND: Notch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways. RESULTS: We show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells (by the insulin pathway), in T-cells (via TCR activation) or in neurons (via TrKB activation) potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals. CONCLUSION: The PI3K-Akt pathway acts as a "gain control" for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses.}, address = {Lorantis Ltd., Cambridge, CB4 0PE, UK. grahame.mckenzie@inion.com}, author = {McKenzie, G. and Ward, G. and Stallwood, Y. and Briend, E. and Papadia, S. and Lennard, A. and Turner, M. and Champion, B. and Hardingham, G. E.}, citeulike-article-id = {599318}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2121-7-10}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16507111}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16507111}, doi = {10.1186/1471-2121-7-10}, issn = {1471-2121}, journal = {BMC Cell Biol}, keywords = {akt, notch, pi3k}, posted-at = {2006-04-25 08:54:47}, priority = {5}, title = {Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals.}, url = {http://dx.doi.org/10.1186/1471-2121-7-10}, volume = {7}, year = {2006} }

TY - JOUR ID - citeulike:599318 L3 - citeulike-article-id:599318 N2 - BACKGROUND: Notch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways. RESULTS: We show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells (by the insulin pathway), in T-cells (via TCR activation) or in neurons (via TrKB activation) potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals. CONCLUSION: The PI3K-Akt pathway acts as a "gain control" for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses. JF - BMC Cell Biol SN - 1471-2121 AD - Lorantis Ltd., Cambridge, CB4 0PE, UK. grahame.mckenzie@inion.com TI - Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals. VL - 7 KW - akt KW - notch KW - pi3k AU - McKenzie, G AU - Ward, G AU - Stallwood, Y AU - Briend, E AU - Papadia, S AU - Lennard, A AU - Turner, M AU - Champion, B AU - Hardingham, GE PY - 2006/// UR - http://dx.doi.org/10.1186/1471-2121-7-10 ER -