PXD050817

PXD050817 is an original dataset announced via ProteomeXchange.

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 p85levels observed in cancer, enhances cell growth and tumorsphere formation, and these effects are abrogated by MAP4 or p85knockdown, underscoring their role in the tumor-promoting activity of p85loss.
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

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-20 08:03:34	ID requested
⏵ 1	2024-10-17 05:06:22	announced

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;

submitter keyword: p85,PI3K, Akt, endosomes, p110, MAP4, PI3P

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

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PRIDE project URI

• PRIDE
  1. PXD050817
     1. Label: PRIDE project
     2. Name: A p85 Isoform Switch Enhances PI3K Activation on Endosomes by a MAP4- and PI3P-dependent Mechanism