References

Apsel B., Blair J.A., Gonzalez B., Nazif T.M., Feldman M.E., Aizenstein B., Hoffman R., Williams R.L., Shokat K.M. & Knight Z.A. 2008. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat. Chem. Biol. 4: 691–699.10.1038/nchembio.117Search in Google Scholar PubMed PubMed Central

Avruch J., Hara K., Lin Y., Liu M., Long X., Ortiz-Vega S. & Yonezawa K. 2006. Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase. Oncogene 25: 6361–6372.10.1038/sj.onc.1209882Search in Google Scholar PubMed

Bang O.S., Kim E.J., Chung J.G., Lee S.R., Park T.K. & Kang S.S. 2000. Association of focal adhesion kinase with fibronectin and paxillin is required for precartilage condensation of chick mesenchymal cells. Biochem. Biophys. Res. Commun. 278: 522–529.10.1006/bbrc.2000.3831Search in Google Scholar PubMed

Bertrand L., Horman S., Beauloye C. & Vanoverschelde J.L. 2008. Insulin signalling in the heart. Cardiovasc. Res. 79: 238–248.10.1093/cvr/cvn093Search in Google Scholar PubMed

Berven L.A. & Crouch M.F. 2000. Cellular function of p70S6K: a role in regulating cell motility. Immunol. Cell Biol. 78: 447–451.10.1046/j.1440-1711.2000.00928.xSearch in Google Scholar PubMed

Cantley L.C. 2002. The phosphoinositide 3-kinase pathway. Science 296: 1655–1657.10.1126/science.296.5573.1655Search in Google Scholar PubMed

Copp J., Manning G. & Hunter T. 2009. TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res. 69: 1821–1827.10.1158/0008-5472.CAN-08-3014Search in Google Scholar PubMed PubMed Central

Corradetti M.N. & Guan K.L. 2006. Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene 25: 6347–6360.10.1038/sj.onc.1209885Search in Google Scholar PubMed

Finlay D.K., Rosenzweig E., Sinclair L.V., Feijoo-Carnero C., Hukelmann J.L., Rolf J., Panteleyev A.A., Okkenhaug K. & Cantrell D.A. 2012. PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J. Exp. Med. 209: 2441–2453.10.1084/jem.20112607Search in Google Scholar PubMed PubMed Central

Fujita T., Fukuyama R., Enomoto H. & Komori T. 2004. Dexamethasone inhibits insulin-induced chondrogenesis of ATDC5 cells by preventing PI3K-Akt signaling and DNA binding of Runx2. J. Cell. Biochem. 93: 374–383.10.1002/jcb.20192Search in Google Scholar PubMed

Gayer C.P., Chaturvedi L.S., Wang S., Craig D.H., Flanigan T. & Basson M.D. 2009. Strain-induced proliferation requires thse phosphatidylinositol 3-kinase/AKT/glycogen synthase kinase pathway. J. Biol. Chem. 284: 2001–2011.10.1074/jbc.M804576200Search in Google Scholar

Greiwe J.S., Kwon G., McDaniel M.L. & Semenkovich C.F. 2001. Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 281: E466–E471.10.1152/ajpendo.2001.281.3.E466Search in Google Scholar

Guan Y., Yang X., Yang W., Charbonneau C. & Chen Q. 2014. Mechanical activation of mammalian target of rapamycin pathway is required for cartilage development. FASEB J. 28: 4470–4481.10.1096/fj.14-252783Search in Google Scholar

Hay N. & Sonenberg N. 2004. Upstream and downstream of mTOR. Genes Dev. 18: 1926–1945.10.1101/gad.1212704Search in Google Scholar

Hidaka K., Kanematsu T., Takeuchi H., Nakata M., Kikkawa U. & Hirata M. 2001. Involvement of the phosphoinositide 3-kinase/protein kinase B signaling pathway in insulin/IGF-I-induced chondrogenesis of the mouse embryonal carcinomaderived cell line ATDC5. Int. J. Biochem. Cell Biol. 33: 1094–1103.10.1016/S1357-2725(01)00067-XSearch in Google Scholar

Hirsch E., Costa C. & Ciraolo E. 2007. Phosphoinositide 3-kinases as a common platform for multi-hormone signaling. J. Endocrinol. 194: 243–256.10.1677/JOE-07-0097Search in Google Scholar PubMed

Hoshino Y., Nishimura K. & Sumpio B.E. 2007. Phosphatase PTEN is inactivated in bovine aortic endothelial cells exposed to cyclic strain. J. Cell. Biochem. 100: 515–526.10.1002/jcb.21085Search in Google Scholar PubMed

Katso R., Okkenhaug K., Ahmadi K., White S., Timms J. & Waterfield M.D. 2001. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu. Rev. Cell Dev. Biol. 17: 615–675.10.1146/annurev.cellbio.17.1.615Search in Google Scholar PubMed

Kim M.J., Kim S., Kim Y., Jin E.J. & Sonn J.K. 2012. Inhibition of RhoA but not ROCK induces chondrogenesis of chick limb mesenchymal cells. Biochem. Biophys. Res. Commun. 418: 500–505.10.1016/j.bbrc.2012.01.053Search in Google Scholar PubMed

Krasilnikov M.A. 2000. Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. Biochemistry (Moscow) 65: 59–67.Search in Google Scholar

Krause U., Bertrand L., Maisin L., Rosa M. & Hue L. 2002. Signalling pathways and combinatory effects of insulin and amino acids in isolated rat hepatocytes. Eur. J. Biochem. 269: 3742–3750.10.1046/j.1432-1033.2002.03069.xSearch in Google Scholar PubMed

Langelier E., Suetterlin R., Hoemann C.D., Aebi U. & Buschmann M.D. 2000. The chondrocyte cytoskeleton in mature articular cartilage: structure and distribution of actin, tubulin, and vimentin filaments. J. Histochem. Cytochem. 48: 1307–1320.10.1177/002215540004801002Search in Google Scholar

Lee H.H., Chang C.C., Shieh M.J., Wang J.P., Chen Y.T., Young T.H. & Hung S.C. 2013. Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect. Sci. Rep. 3: 2683.10.1038/srep02683Search in Google Scholar

Lim Y.B., Kang S.S., Park T.K., Lee Y.S., Chun J.S. & Sonn J.K. 2000. Disruption of actin cytoskeleton induces chondrogenesis of mesenchymal cells by activating protein kinase C-alpha signaling. Biochem. Biophys. Res. Commun. 273: 609–613.10.1006/bbrc.2000.2987Search in Google Scholar

Mora A., Komander D., van Aalten D.M. & Alessi D.R. 2004. PDK1, the master regulator of AGC kinase signal transduction. Semin. Cell Dev. Biol. 15: 161–170.10.1016/j.semcdb.2003.12.022Search in Google Scholar

Najafov A., Sommer E.M., Axten J.M., Deyoung M.P. & Alessi D.R. 2011. Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1. Biochem. J. 433: 357–369.10.1042/BJ20101732Search in Google Scholar

Oh C.D. & Chun J.S. 2003. Signaling mechanisms leading to the regulation of differentiation and apoptosis of articular chondrocytes by insulin-like growth factor-1. J. Biol. Chem. 278: 36563–36571.10.1074/jbc.M304857200Search in Google Scholar

Oh C.D., Kim S.J., Ju J.W., Song W.K., Kim J.H., Yoo Y.J. & Chun J.S. 2001. Immunosuppressant rapamycin inhibits protein kinase C alpha and p38 mitogen-activated protein kinase leading to the inhibition of chondrogenesis. Eur. J. Pharmacol. 427: 175–185.10.1016/S0014-2999(01)01241-9Search in Google Scholar

Park E.H., Kang S.S., Lee Y.S., Kim S.J., Jin E.J., Tak E.N. & Sonn J.K. 2008. Integrity of the cortical actin ring is required for activation of the PI3K/Akt and p38 MAPK signaling pathways in redifferentiation of chondrocytes on chitosan. Cell Biol. Int. 32: 1272–1278.10.1016/j.cellbi.2008.07.013Search in Google Scholar PubMed

Peyrollier K., Hajduch E., Blair A.S., Hyde R. & Hundal H.S. 2000. L-leucine availability regulates phosphatidylinositol 3-kinase, p70 S6 kinase and glycogen synthase kinase-3 activity in L6 muscle cells: evidence for the involvement of the mammalian target of rapamycin (mTOR) pathway in the L-leucine-induced up-regulation of system A amino acid transport. Biochem. J. 350: 361–368.10.1042/bj3500361Search in Google Scholar

Phornphutkul C., Lee M., Voigt C., Wu K.Y., Ehrlich M.G., Gruppuso P.A. & Chen Q. 2009. The effect of rapamycin on bone growth in rabbits. J. Orthop. Res. 27: 1157–1161.10.1002/jor.20894Search in Google Scholar PubMed PubMed Central

Phornphutkul C., Wu K.Y., Auyeung V., Chen Q. & Gruppuso P.A. 2008. mTOR signaling contributes to chondrocyte differentiation. Dev. Dyn. 237: 702–712.10.1002/dvdy.21464Search in Google Scholar

Qian Y., Corum L., Meng Q., Blenis J., Zheng J.Z., Shi X., Flynn D.C. & Jiang B.H. 2004. PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration. Am. J. Physiol. 286: C153–C163.10.1152/ajpcell.00142.2003Search in Google Scholar

Rodriguez-Viciana P., Warne P.H., Dhand R., Vanhaesebroeck B., Gout I., Fry M.J., Waterfield M.D. & Downward J. 1994. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 370: 527–532.10.1038/370527a0Search in Google Scholar

Sanez Canedo C., Demeulder B., Ginion A., Bayascas J.R., Balligand J.L., Alessi D.R., Vanoverschelde J.L., Beauloye C., Hue L. & Bertrand L. 2010. Activation of the cardiac mTOR/p70(S6K) pathway by leucine requires PDK1 and correlates with PRAS40 phosphorylation. Am. J. Physiol. Endocrinol. Metab. 298: E761–E769.10.1152/ajpendo.00421.2009Search in Google Scholar

Sarbassov D.D., Ali S.M. & Sabatini D.M. 2005. Growing roles for the mTOR pathway. Curr. Opin. Cell Biol. 17: 596–603.10.1016/j.ceb.2005.09.009Search in Google Scholar

Slomovitz B.M. & Coleman R.L. 2012. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin. Cancer Res. 18: 5856–5864.10.1158/1078-0432.CCR-12-0662Search in Google Scholar

Solursh M., Linsenmayer T.F. & Jensen K.L. 1982. Chondrogenesis from single limb mesenchyme cells. Dev. Biol. 94: 259–264.10.1016/0012-1606(82)90090-2Search in Google Scholar

Song G., Ouyang G. & Bao S. 2005. The activation of Akt/PKB signaling pathway and cell survival. J. Cell. Mol. Med.9: 59–71.10.1111/j.1582-4934.2005.tb00337.xSearch in Google Scholar

Straight A.F., Cheung A., Limouze J., Chen I., Westwood N.J., Sellers J.R. & Mitchison T.J. 2003. Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor. Science 299: 1743–1747.10.1126/science.1081412Search in Google Scholar

Tsakiridis T., Tong P., Matthews B., Tsiani E., Bilan P.J., Klip A. & Downey G.P. 1999. Role of the actin cytoskeleton in insulin action. Microsc. Res. Tech. 47: 79–92.10.1002/(SICI)1097-0029(19991015)47:2<79::AID-JEMT1>3.0.CO;2-SSearch in Google Scholar

Vanhaesebroeck B. & Alessi D.R. 2000. The PI3K-PDK1 connection: more than just a road to PKB. Biochem. J. 346: 561–576.10.1042/bj3460561Search in Google Scholar

Wennström S., Hawkins P., Cooke F., Hara K., Yonezawa K., Kasuga M., Jackson T., Claesson-Welsh L. & Stephens L. 1994. Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling. Curr. Biol. 4: 385–393.10.1016/S0960-9822(00)00087-7Search in Google Scholar

Wezeman F.H. 1998. Morphological foundations of precartilage development in mesenchyme. Microsc. Res. Tech. 43: 91–101.10.1002/(SICI)1097-0029(19981015)43:2<91::AID-JEMT2>3.0.CO;2-3Search in Google Scholar

Zanetti N.C. & Solursh M. 1984. Induction of chondrogenesis in limb mesenchymal cultures by disruption of the actin cytoskeleton. J. Cell Biol. 99: 115–123.10.1083/jcb.99.1.115Search in Google Scholar