PXD038649-1

PXD038649 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-07 08:01:18	ID requested
⏵ 1	2022-12-21 03:55:07	announced

Dataset with its publication pending

submitter keyword: phosphoproteomics, IR, insulin, IGFR

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

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PRIDE project URI

• PRIDE
  1. PXD038649
     1. Label: PRIDE project
     2. Name: Leucine-973 is a Crucial Residue Differentiating Insulin and IGF-1 Receptor Signaling