PXD032397

PXD032397 is an original dataset announced via ProteomeXchange.

Title	Quantitative phosphoproteomic analysis of human Arl4A upon fibronectin stimulation
Description	The extracellular matrix (ECM) fibronectin (FN) not only provides the framework for cell invasion and deposition of collagens and other ECMs from wound studies, but also guide collective tumor migration during cancer progression. p21-activated kinase 1 (Pak1) and Arf-like (Arl) GTPase Arl4A have previously been found to recruit each other on the plasm membrane to promote cell migration, and their plasma membrane translocation are robustly potentiated by FN. Under FN stimulation, we found that Pak1 kinase activity is required for Arl4A protein stabilization. How FN-induced Pak1 activity enhances Arl4A protein stability is unknown. Given that the Pak1-Arl4A interaction is direct, we hypothesized that alternation of Pak1-dependent phosphorylation on Arl4A leads to its protein stabilization upon FN stimulation. We herein applied the SILAC method to identify the phosphorylation sites on Arl4A upon FN treatment through MS analysis and found that S141/143 site(s) increased phosphorylation under FN stimulation. We further validated that phosphorylation on S143 of Arl4A and corresponding site on S144 of Arl4D (closest Arl member of Arl4A) are indeed dependent on Pak1 kinase and contribute to their protein stability. By dissecting the phosphorylation property on S143/S144 of Arl4A/D, we revealed an Arl4A/D specific chaperon protein HYPK as the underlying mechanism to mask and protect the phospho-form of Arl4A/D from fast proteasome degradation. This study provides how FN signaling cascade promotes cell migration on a molecular basis by regulating Arl4A/D phosphorylation.
HostingRepository	PRIDE
AnnounceDate	2022-07-29
AnnouncementXML	Submission_2022-07-28_18:29:28.581.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chia-Jung Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; 6x(13)C labeled residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-18 09:09:31	ID requested
⏵ 1	2022-07-28 18:29:29	announced

Lin MC, Yu CJ, Lee FS, Phosphorylation of Arl4A/D promotes their binding by the HYPK chaperone for their stable recruitment to the plasma membrane. Proc Natl Acad Sci U S A, 119(30):e2207414119(2022) [pubmed]

submitter keyword: Fibronectin, Pak1, Arf-like GTPase, Arl4A, HYPK

Chia-Jung Yu
contact affiliation	Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
contact email	yucj1124@mail.cgu.edu.tw
lab head
Chia-Jung Yu
contact affiliation	Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
contact email	yucj1124@mail.cgu.edu.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032397
     1. Label: PRIDE project
     2. Name: Quantitative phosphoproteomic analysis of human Arl4A upon fibronectin stimulation