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PXD038649-1

PXD038649 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLeucine-973 is a Crucial Residue Differentiating Insulin and IGF-1 Receptor Signaling
DescriptionInsulin 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.
HostingRepositoryPRIDE
AnnounceDate2022-12-21
AnnouncementXMLSubmission_2022-12-21_03:55:07.083.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMartinSteger
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-12-07 08:01:18ID requested
12022-12-21 03:55:07announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: phosphoproteomics, IR, insulin, IGFR
Contact List
RonaldKahn
contact affiliationSection of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
contact emailc.ronald.kahn@joslin.harvard.edu
lab head
MartinSteger
contact affiliationNEOsphere Biotechnologies
contact emailmedusm@hotmail.com
dataset submitter
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Dataset FTP location
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