Jonathan M. Backer
Showed that the class III PI 3-kinase hVps34, best known for its role in autophagy, is regulated by nutrients and is needed for amino acids to activate S6 kinase through mTOR, in parallel with George Thomas's group
Professor of Molecular Pharmacology and of Biochemistry · Chair, Department of Molecular Pharmacology · William S. Lasdon Chair in Pharmacology · Associate Director of Shared Resources, Montefiore Einstein Comprehensive Cancer Center · Albert Einstein College of Medicine, Bronx, NY
Portrait: Albert Einstein College of Medicine
Backer's laboratory works on phosphoinositide kinases — the enzymes that mark membranes with lipid tags and thereby decide which proteins get recruited where. Most of the pathway's attention goes to class I PI3K, the one insulin switches on. His senior-authored contribution to this Atlas is about the other one: hVps34, the class III enzyme that supplies most of the cell's PI(3)P and is best known for building the autophagosome. Class II PI3Ks make PI(3)P as well, at other membranes, so hVps34 is the main source rather than the only one.
BYF2005 put hVps34 upstream of mTORC1 and showed it responds to amino acid and glucose supply rather than to insulin. Published within weeks of a paper from George Thomas's group reaching the same conclusion by a different route (NOB2005), it opened a second account of how amino acids reach mTORC1 — one that has never been fully reconciled with the Rag/Ragulator story that later dominated the field. The Atlas keeps both, because the corpus contains both.
The rest of the laboratory's work is on how altered PI3K regulation drives cancer, with emphasis on breast cancer invasion and metastasis, on macropinocytosis, and on S100A4 signalling in macrophages.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2005 | M | hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase BYF2005 Senior author: hVps34 is a nutrient-regulated lipid kinase required for S6K1 activation, distinct from the insulin input. |
| 2005 | M | Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase NOB2005 The companion paper to BYF2005, from a different laboratory: the amino acid input to mTORC1 is separate from the insulin input and runs through class 3 PI3K (hVps34), not through class 1 PI3K. Historically important because it states that the amino acid branch is the older one and that insulin signalling was grafted onto it. Boundary: cell lines, pharmacological and knockdown evidence; the later Rag/Ragulator account describes a different route to the same target and the two have never been fully reconciled. |
Co-authors in the Atlas
People with a profile here who share at least one study with Jonathan M. Backer.
- Maya P. Byfield 2 shared studies Showed as first author that the lipid kinase hVps34 is regulated by nutrients and is needed for amino acids to activate S6 kinase through mTOR, in parallel with a study from George Thomas's group
- Takahiro Nobukuni Showed as first author that amino acids activate mTOR through the lipid kinase hVps34, by a route separate from insulin signalling through TSC, in parallel with a study from Jonathan Backer's laboratory