Johns Hopkins University

Dana-farber-cancer Institute Inc.

Whitehead Institute for Biomedical Research

David M Sabatini

Solomon H Snyder

Nathanael S Gray

Jae Won Chang

Jianming Zhang

Paul J Tempst

Shomit Sengupta

Qingsong Liu

Hediye Erdjument-Bromage

Mary Lui

Robert A Saxton

Carson C Thoreen

Seong Woo Anthony Kang

Lynne Chantranupong

Jose Orozco

Shuyu Wang

Zhi Tsun

Rachel L Wolfson

Jason Cantor

A protein complex containing 245 kDa and 35 kDa components, designated RAFT1 and RAFT2 (for apamycin nd KBP12 arget) interacts with FKBP12 in a rapamycin-dependent manner. This interaction has the pharmacological characteristics expected from the observed in vivo effects of rapamycin: it occurs at low nanomolar concentrations of rapamycin and is competed by excess FK506. Sequences (330 amino acids total) of tryptic peptides derived from the affinity purified 245 kDa RAFT1 reveals striking homologies to the predicted products of the yeast TOR genes, which were originally identified by mutations that confer rapamycin resistance in yeast. A RAFT1 cDNA was obtained and found to encode a 289 kDa protein (2550 amino acids) that is 43% and 39% identical to TOR2 and TOR1, respectively.

Mammalian proteins that bind to FKBP12 in a rapamycin-dependent fashion

A protein complex containing 245 kDa and 35 kDa components, designated RAFT1 and RAFT2 (for Rapamycin And FKBP12 Target) interacts with FKBP12 in a rapamycin-dependent manner. This interaction has the pharmacological characteristics expected from the observed in vivo effects of rapamycin: it occurs at low nanomolar concentrations of rapamycin and is competed by excess FK506. Sequences (330 amino acids total) of tryptic peptides derived from the affinity purified 245 kDa RAFT1 reveals striking homologies to the predicted products of the yeast TOR genes, which were originally identified by mutations that confer rapamycin resistance in yeast. A RAFT1 cDNA was obtained and found to encode a 289 kDa protein (2550 amino acids) that is 43% and 39% identical to TOR2 and TOR1, respectively.

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Baltimore, MD, United States of America

David M Sabatini