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Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20\u2010fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance.\n                  <\/jats:p>","DOI":"10.15252\/msb.20156250","type":"journal-article","created":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T21:19:28Z","timestamp":1437599968000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic variation in insulin\u2010induced kinase signaling"],"prefix":"10.1038","volume":"11","author":[{"given":"Isabel Xiaorong","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girish","family":"Ramrattan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian G","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,7,22]]},"reference":[{"key":"BFMSB156250_CR1","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1172\/JCI116066","volume":"90","author":"K Aalto\u2010Set\u00e4l\u00e4","year":"1992","unstructured":"Aalto\u2010Set\u00e4l\u00e4 K, Fisher EA, Chen X, Chajek\u2010Shaul T, Hayek T, Zechner R, Walsh A, Ramakrishnan R, Ginsberg HN, Breslow JL (1992) Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. 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