@article{wang_cirit_haugh_2011, title={PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk (vol 5, pg 246, 2009)}, volume={7}, ISSN={["1744-4292"]}, DOI={10.1038/msb.2011.61}, number={1}, journal={MOLECULAR SYSTEMS BIOLOGY}, publisher={Wiley-Blackwell}, author={Wang, Chun-Chao and Cirit, Murat and Haugh, Jason M.}, year={2011}, month={Aug} }
 @article{cirit_wang_haugh_2010, title={Systematic Quantification of Negative Feedback Mechanisms in the Extracellular Signal-regulated Kinase (ERK) Signaling Network}, volume={285}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.m110.148759}, abstractNote={Cell responses are actuated by tightly controlled signal transduction pathways. Although the concept of an integrated signaling network replete with interpathway cross-talk and feedback regulation is broadly appreciated, kinetic data of the type needed to characterize such interactions in conjunction with mathematical models are lacking. In mammalian cells, the Ras/ERK pathway controls cell proliferation and other responses stimulated by growth factors, and several cross-talk and feedback mechanisms affecting its activation have been identified. In this work, we take a systematic approach to parse the magnitudes of multiple regulatory mechanisms that attenuate ERK activation through canonical (Ras-dependent) and non-canonical (PI3K-dependent) pathways. In addition to regulation of receptor and ligand levels, we consider three layers of ERK-dependent feedback: desensitization of Ras activation, negative regulation of MEK kinase (e.g. Raf) activities, and up-regulation of dual-specificity ERK phosphatases. Our results establish the second of these as the dominant mode of ERK self-regulation in mouse fibroblasts. We further demonstrate that kinetic models of signaling networks, trained on a sufficient diversity of quantitative data, can be reasonably comprehensive, accurate, and predictive in the dynamical sense.}, number={47}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, publisher={American Society for Biochemistry & Molecular Biology (ASBMB)}, author={Cirit, Murat and Wang, Chun-Chao and Haugh, Jason M.}, year={2010}, month={Nov}, pages={36736–36744} }
 @article{weiger_wang_krajcovic_melvin_rhoden_haugh_2009, title={Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts}, volume={122}, ISSN={["1477-9137"]}, DOI={10.1242/jcs.037564}, abstractNote={During directed cell migration (chemotaxis), cytoskeletal dynamics are stimulated and spatially biased by phosphoinositide 3-kinase (PI3K) and other signal transduction pathways. Live-cell imaging using total internal reflection fluorescence (TIRF) microscopy revealed that, in the absence of soluble cues, 3′-phosphoinositides are enriched in a localized and dynamic fashion during active spreading and random migration of mouse fibroblasts on adhesive surfaces. Surprisingly, we found that PI3K activation is uncoupled from classical integrin-mediated pathways and feedback from the actin cytoskeleton. Inhibiting PI3K significantly impairs cell motility, both in the context of normal spreading and when microtubules are dissociated, which induces a dynamic protrusion phenotype as seen by TIRF in our cells. Accordingly, during random migration, 3′-phosphoinositides are frequently localized to regions of membrane protrusion and correlate quantitatively with the direction and persistence of cell movement. These results underscore the importance of localized PI3K signaling not only in chemotaxis but also in basal motility/migration of fibroblasts.}, number={3}, journal={JOURNAL OF CELL SCIENCE}, publisher={The Company of Biologists}, author={Weiger, Michael C. and Wang, Chun-Chao and Krajcovic, Matej and Melvin, Adam T. and Rhoden, John J. and Haugh, Jason M.}, year={2009}, month={Feb}, pages={313–323} }