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The Src homology\u20102 domain containing protein tyrosine phosphatase 2 (SHP2), encoded by protein tyrosine phosphatase, non\u2010receptor type 11\n                    <jats:italic>(Ptpn11),<\/jats:italic>\n                    is a positive mediator required for most, if not all, receptor tyrosine kinase\u2013evoked RAS\/ERK activation, but differentially regulates the PI3K\/AKT signaling cascade in various cellular contexts. The precise mechanisms underlying the differential effects of SHP2 deficiency on the PI3K pathway remain unclear. We found that mice with myelomonocytic cell\u2010specific [\n                    <jats:italic>\n                      Tg(LysM\u2010Cre);Ptpn11\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice]\n                    <jats:italic>Ptpn11<\/jats:italic>\n                    deficiency exhibit mild osteopetrosis. SHP2\u2010deficient bone marrow macrophages (BMMs) showed decreased proliferation in response to M\u2010CSF and decreased osteoclast generation. M\u2010CSF\u2013evoked ERK1\/2 activation was decreased, whereas AKT activation was enhanced in SHP2\u2010deficient BMMs. ERK1\/2,\n                    <jats:italic>via<\/jats:italic>\n                    its downstream target RSK2, mediates this negative feedback by negatively regulating phosphorylation of M\u2010CSF receptor at Tyr721 and, consequently, its binding to p85 subunit of PI3K and PI3K activation. Pharmacologic inhibition of RSK or ERK phenotypically mimics the signaling defects observed in SHP2\u2010deficient BMMs. Furthermore, this increase in PI3K\/AKT activation enables BMM survival in the setting of SHP2 deficiency.\u2014Wang, L., Iorio, C., Yan, K., Yang, H., Takeshita, S., Kang, S., Neel, B.G., Yang, W. An ERK\/RSK\u2010mediated negative feedback loop regulates M\u2010CSF\u2010evoked PI3K\/AKT activation in macrophages.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 875\u2013887 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700672rr","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T15:55:13Z","timestamp":1508342113000},"page":"875-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["A ERK\/RSK\u2010mediated negative feedback loop regulates M\u2010CSF\u2013evoked PI3K\/AKT activation in macrophages"],"prefix":"10.1096","volume":"32","author":[{"given":"Lijun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Brown University Alpert 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