PXD036069-2

PXD036069 is an original dataset announced via ProteomeXchange.

Title	Phosphosecretome profiling and kinase-substrate interaction screening reveal key extracellular c-Src-regulated pathways
Description	Secreted protein kinases are responsible for the phosphorylation of a vast number of extracellular phosphoproteins. The tyrosine kinase c-Src is secreted through the vesicular trafficking pathway, however, mechanistic insights into extracellular substrate specificity and potential therapeutic opportunities in cancer remain unexplored. Here, we show that the SH4/Unique region of c-Src is required for its secretion. Limited proteolysis-mass spectrometry together with mutagenesis further confirmed predictions of in-silico molecular docking of active c-Src structure with its bona fide substrate TIMP2, that the Src homology 3 (SH3) domain is critical for kinase interaction with the P31xxP34 motif in the amino domain of TIMP2. Interestingly, comprehensive unbiased phosphoproteomic studies revealed an enrichment of PxxP containing extracellular substrates as potential targets of secreted c-Src. Cell-based studies using custom anti-c-Src antibodies against the c-Src SH3-TIMP2 interacting interface revealed that blocking secreted Src not only disrupts kinase-substrate interaction but also inhibits prostate cancer cell proliferation. Together, our data provide insights into the intricate role of secreted c-Src in extracellular phosphorylation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:51.377.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sarah Backe
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-16 05:24:57	ID requested
1	2023-05-30 09:57:15	announced
⏵ 2	2023-11-14 08:57:51	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: post translational modification, The tissue inhibitors of metalloproteinases, PxxP motif, Src tyrosine kinase, TIMPs, tumor growth inhibition,Phosphoproteomic, blocking antibodies, secretome

Dimitra Bourboulia
contact affiliation	Department of Urology, SUNY Upstate Medical University Syracuse, NY 13210, USA
contact email	bourmpod@upstate.edu
lab head
Sarah Backe
contact affiliation	SUNY Upstate Medical University
contact email	backes@upstate.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036069
     1. Label: PRIDE project
     2. Name: Phosphosecretome profiling and kinase-substrate interaction screening reveal key extracellular c-Src-regulated pathways