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Janice D. Thomas
M.S., Montclair State University – 2006
Thesis Advisor: X.F. Steven Zheng, Ph.D.
Graduate Program in Cellular & Molecular Pharmacology
Pharmacology Department Room 517
RWJMS Research Tower
Monday, April 16, 2012
The mTORC1 protein kinase complex plays a central role in two pathways that regulate cell growth and proliferation in response to the presence of amino acids and growth factors. It has been well established that hyperactivation of these pathways is found in many common cancers. We find that the small guanosine triphosphatase Rab1 proteins, both isoforms A and B, interact with mTORC1 in an amino acid sensitive manner and are necessary for the activation of the mTORC1 pathway by amino acids in a Rag GTPase independent manner. A Rab1 mutant that is constitutively bound to guanosine triphosphate interacted strongly with mTORC1, and its expression within cells increased mTORC1 signaling. Conversely, expression of a guanosine diphosphate bound Rab1 mutant decreased mTORC1 signaling. Although mTORC1 is not stimulated directly by Rab1, the intracellular localization of mTORC1 is directed to the Golgi apparatus by Rab1 under amino acid stimulation, an integral component of the endosomal compartment which also contains its activator Rheb1.