Ras signalling on the endoplasmic reticulum and the Golgi.
Current models evoke the plasma membrane (PM) as the exclusive platform from which Ras regulates signalling. We developed a fluorescent probe that reports where and when Ras is activated in living cells. We show that oncogenic H-Ras and N-Ras engage Raf-1 on the Golgi and that endogenous Ras and unpalmitoylated H-Ras are activated in response to mitogens on the Golgi and endoplasmic reticulum (ER), respectively. We also demonstrate that H-Ras that is restricted to the ER can activate the Erk pathway and transform fibroblasts, and that Ras localized on different membrane compartments differentially engages various signalling pathways. Thus, Ras signalling is not limited to the PM, but also proceeds on the endomembrane.
Chiu
Vi K
VK
Department of Medicine, Cell Biology and Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Bivona
Trever
T
Hach
Angela
A
Sajous
J Bernard
JB
Silletti
Joseph
J
Wiener
Heidi
H
Johnson
Ronald L
RL
Cox
Adrienne D
AD
Philips
Mark R
MR
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004735:Energy Transfer; D017930:Genes, Reporter; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D006133:Growth Substances; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D019061:src-Family Kinases; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins