An in vitro method of (i) producing induced pluripotent stem cells or (ii) improving the efficiency of establishment of induced pluripotent stem cells, the method comprising contacting a somatic cell with nuclear reprogramming substances and one or more exogenous factors that activate a signal transmission pathway including Ras, PI3 kinase, AKT, Rheb, mTOR and S6K1, wherein the exogenous factors are selected from the group consisting of the following to : V12Y40C mutants of HRas, NRas and KRas; constitutively active mutants of PI3 kinase wherein a membrane localization signal sequence is added to their N-terminal or C-terminal; constitutively active mutants of Akt1, Akt2 and Akt3 wherein a membrane localization signal sequence is added to their N-terminal or C-terminal; Rheb and T389E mutant of S6K1; PTEN shRNA; and nucleic acids that encode to above, and wherein the nuclear reprogramming substances comprise any of the following (a) to (g): (a) Oct3/4, Sox2 and Klf4, (b) (i) Oct3/4, (ii) a member of Sox family selected from the group consisting of Sox1, Sox2, Sox3, Sox15, Sox17 and Sox18, (iii) a member of Klf family selected from the group consisting of Klf1, Klf2, Klf4 and Klf5, and (iv) a member of Myc family selected from the group consisting of c-Myc, T58A (activated mutant of c-Myc) and L-Myc, (c) Oct3/4 and Sox2, (d) Oct3/4, Sox2 and Nanog, (e) Oct3/4, Sox2 and Lin28, (f) Oct3/4, Sox2, Nanog and Lin28, and (g) nucleic acids that encode any of (a) to (f) above. V12Y40C mutants of HRas, NRas and KRas; constitutively active mutants of PI3 kinase wherein a membrane localization signal sequence is added to their N-terminal or C-terminal; constitutively active mutants of Akt1, Akt2 and Akt3 wherein a membrane localization signal sequence is added to their N-terminal or C-terminal; Rheb and T389E mutant of S6K1; PTEN shRNA; and nucleic acids that encode to above, and wherein the nuclear reprogramming substances comprise any of the following (a) to (g): (a) Oct3/4, Sox2 and Klf4, (b) (i) Oct3/4, (ii) a member of Sox family selected from the group consisting of Sox1, Sox2, Sox3, Sox15, Sox17 and Sox18, (iii) a member of Klf family selected from the group consisting of Klf1, Klf2, Klf4 and Klf5, and (iv) a member of Myc family selected from the group consisting of c-Myc, T58A (activated mutant of c-Myc) and L-Myc, (c) Oct3/4 and Sox2, (d) Oct3/4, Sox2 and Nanog, (e) Oct3/4, Sox2 and Lin28, (f) Oct3/4, Sox2, Nanog and Lin28, and (g) nucleic acids that encode any of (a) to (f) above. (a) Oct3/4, Sox2 and Klf4, (b) (i) Oct3/4, (ii) a member of Sox family selected from the group consisting of Sox1, Sox2, Sox3, Sox15, Sox17 and Sox18, (iii) a member of Klf family selected from the group consisting of Klf1, Klf2, Klf4 and Klf5, and (iv) a member of Myc family selected from the group consisting of c-Myc, T58A (activated mutant of c-Myc) and L-Myc, (i) Oct3/4, (ii) a member of Sox family selected from the group consisting of Sox1, Sox2, Sox3, Sox15, Sox17 and Sox18, (iii) a member of Klf family selected from the group consisting of Klf1, Klf2, Klf4 and Klf5, and (iv) a member of Myc family selected from the group consisting of c-Myc, T58A (activated mutant of c-Myc) and L-Myc, (c) Oct3/4 and Sox2, (d) Oct3/4, Sox2 and Nanog, (e) Oct3/4, Sox2 and Lin28, (f) Oct3/4, Sox2, Nanog and Lin28, and (g) nucleic acids that encode any of (a) to (f) above. <EOS>