PXD050817
PXD050817 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | A p85 Isoform Switch Enhances PI3K Activation on Endosomes by a MAP4- and PI3P-dependent Mechanism |
Description | PI3K is a heterodimer of p110 catalytic and p85 adaptor subunits that is activated by agonist-stimulated receptor tyrosine kinases. Although p85 recruits p110 to activated receptors on membranes, p85 loss, which occurs commonly in cancer, paradoxically promotes agonist-stimulated PI3K/Akt signaling. p110 localizes to microtubules via MAP4, facilitating its interaction with activated receptor kinases on endosomes to initiate PI3K/Akt signaling. Here, we demonstrate that in response to agonist stimulation and p85 knock down, the residual p110 coupled predominantly to p85 exhibits enhanced recruitment with receptor tyrosine kinases to endosomes. Moreover, the p110 C2 domain binds PI3P and this interaction is also required to recruit p110 to endosomes and for PI3K/Akt signaling. Stable knockdown of p85, which mimics the reduced p85levels observed in cancer, enhances cell growth and tumorsphere formation, and these effects are abrogated by MAP4 or p85knockdown, underscoring their role in the tumor-promoting activity of p85loss. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-17 |
AnnouncementXML | Submission_2024-10-17_05:06:21.380.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD050817 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Greg Sabat |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-03-20 08:03:34 | ID requested | |
⏵ 1 | 2024-10-17 05:06:22 | announced |
Publication List
10.1016/j.celrep.2024.114119; |
Thapa N, Chen M, Cryns VL, Anderson R, A p85 isoform switch enhances PI3K activation on endosomes by a MAP4- and PI3P-dependent mechanism. Cell Rep, 43(5):114119(2024) [pubmed] |
10.6019/PXD050817; |
Keyword List
submitter keyword: p85,PI3K, Akt, endosomes, p110, MAP4, PI3P |
Contact List
Dr. Richard A Anderson | |
---|---|
contact affiliation | University of Wisconsin School of Medicine and Public Health |
contact email | raanders@wisc.edu |
lab head | |
Greg Sabat | |
contact affiliation | University of Wisconsin |
contact email | gsabat@wisc.edu |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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