TY - JOUR
T1 - Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size
AU - Potter, Christopher J.
AU - Huang, He
AU - Xu, Tian
N1 - Funding Information:
We thank I. Hariharan for exchanging information prior to publication; L. Cooley and K. Wehner for critical readings; E. Hafen, J. Montagne, T. Neufeld, and B. Dickson for fly stocks; R. Carbone for FACS analysis; X. Fei for injections; and H. Chang for pupal dissections. Special thanks to N. Ito for UAS-Tsc2 flies. This work was supported by a grant from NIH (CA69408) to T.X., who is a Howard Hughes Medical Institute Assistant Investigator. C.J.P. is a predoctoral candidate in the Dept. of Genetics.
PY - 2001/5/4
Y1 - 2001/5/4
N2 - Tuberous sclerosis complex is a dominant disorder that leads to the development of benign tumors in multiple organs. We have isolated a mutation in the Drosophila homolog of TSC1 (Tsc1). Cells mutant for Tsc1 are dramatically increased in size yet differentiate normally. Organ size is also increased in tissues that contain a majority of mutant cells. Clones of Tsc1 mutant cells in the imaginal discs undergo additional divisions but retain normal ploidy. We also show that the Tsc1 protein binds to Drosophila Tsc2 in vitro. Overexpression of Tsc1 or Tsc2 alone in the wing and eye has no effect, but co-overexpression leads to a decrease in cell size, cell number, and organ size. Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway.
AB - Tuberous sclerosis complex is a dominant disorder that leads to the development of benign tumors in multiple organs. We have isolated a mutation in the Drosophila homolog of TSC1 (Tsc1). Cells mutant for Tsc1 are dramatically increased in size yet differentiate normally. Organ size is also increased in tissues that contain a majority of mutant cells. Clones of Tsc1 mutant cells in the imaginal discs undergo additional divisions but retain normal ploidy. We also show that the Tsc1 protein binds to Drosophila Tsc2 in vitro. Overexpression of Tsc1 or Tsc2 alone in the wing and eye has no effect, but co-overexpression leads to a decrease in cell size, cell number, and organ size. Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway.
UR - http://www.scopus.com/inward/record.url?scp=0035805162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035805162&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(01)00333-6
DO - 10.1016/S0092-8674(01)00333-6
M3 - Article
C2 - 11348592
AN - SCOPUS:0035805162
SN - 0092-8674
VL - 105
SP - 357
EP - 368
JO - Cell
JF - Cell
IS - 3
ER -