PXD038649 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Leucine-973 is a Crucial Residue Differentiating Insulin and IGF-1 Receptor Signaling |
Description | Insulin and IGF-1 receptors (IR/IGF1R) are highly homologous and share similar signaling systems, but each has a unique physiological role, with IR primarily regulating metabolic homeostasis and IGF1R regulating mitogenic control and growth. Here, we show that replacement of a single amino acid at position 973, just distal to the NPEY motif in the intracellular juxtamembrane region, from leucine, which is highly-conserved in IRs, to phenylalanine, the highly-conserved homologous residue in IGF1Rs, results in decreased IRS-1-PI3K-Akt-mTORC1 signaling and increased of Shc-Gab1-MAPK-cell cycle signaling. As a result, cells expressing L973F-IR exhibit decreased insulin-induced glucose uptake, increased cell growth and impaired receptor internalization. Mice with knockin of the L973F-IR show similar alterations in signaling in vivo, and this leads to decreased insulin sensitivity, a modest increase in growth and decreased weight gain when challenged with high-fat diet. Thus, leucine973 in the juxtamembrane region of the IR acts is a crucial residue differentiating IR signaling from IGF1R signaling. |
HostingRepository | PRIDE |
AnnounceDate | 2022-12-21 |
AnnouncementXML | Submission_2022-12-21_03:55:07.083.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | MartinSteger |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-12-07 08:01:18 | ID requested | |
⏵ 1 | 2022-12-21 03:55:07 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: phosphoproteomics, IR, insulin, IGFR |
Contact List
RonaldKahn |
contact affiliation | Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA |
contact email | c.ronald.kahn@joslin.harvard.edu |
lab head | |
MartinSteger |
contact affiliation | NEOsphere Biotechnologies |
contact email | medusm@hotmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038649
- Label: PRIDE project
- Name: Leucine-973 is a Crucial Residue Differentiating Insulin and IGF-1 Receptor Signaling