Figure 8. Cross talk between Src signaling and methionine-Tor signaling.

(A) An in vitro culture of the wing disc with a methionine analog homopropargylglycine (HPG) demonstrates that the tumor disc induced by Src42A constitutively active (CA) and JNK DN uptakes more methionine than the control disc. (B) Quantification of the HPG intensity in A. Two-tailed unpaired t-test. (C) The amounts of methionine and SAM in the wing discs were measured by LC-MS. The tumor disc induced by Src42A CA and JNK DN contains a higher amount of SAM, whereas the amount of methionine is not significantly different. Methionine flux was calculated as a ratio of SAM and methionine. Two-tailed unpaired t-test. (D) The increase of methionine incorporation in the Src tumor is not mediated by p38. (E) Quantification of the HPG intensity in D. One-way ANOVA with Sidak’s post-test. (F) p38 inhibition does not suppress the upregulated methionine flux by Src42A CA and JNK DN. Two-tailed unpaired t-test. (G) A schematic of the Src42A CA-mediated coupling of cell proliferation and death. JNK activates cell death, while p38 activates cell proliferation, which is regulated by methionine-mediated Tor signaling. Scale bars, 100 µm.

Figure 8—figure supplement 1. Cross-talk between Src signaling and Tor signaling.

(A) The data show the amounts of methionine and SAM in wing discs, which were used to calculate methionine flux in Figure 8F. p38 inhibition does not affect the amounts of methionine and SAM in tumorous discs induced by Src42A constitutively active (CA) and JNK DN. Two-tailed unpaired t-test. (B) A schematic of Src42A CA-mediated Tor regulation. Src activates Tor pathway via both p38-dependent and -independent pathways. Src promotes methionine incorporation and methionine metabolism flux independently of p38, which could activate Tor. On the other hand, Src increases expression of an amino acid transporter, path, in a p38-dependent manner, which could also activate Tor activity through uptake of non-methionine amino acids. (C) RasV12 expression in the wing imaginal disc induces small wings. Knockdown of slpr reverses the wing phenotype induced by RasV12.(D) RasV12 expression in the wing discs induces organismal lethality during development. Knockdown of slpr suppresses organismal lethality induced by RasV12 expression in the wing discs. Two-tailed unpaired t-test. (E) RT-qPCR of amino acid transporters using RNA from wing discs. One-way ANOVA with Sidak’s post-test. (F) RT-qPCR of GATOR1/2 components using RNA from wing discs. One-way ANOVA with Sidak’s post-test.