PhosY-secretome profiling combined with kinase-substrate interaction screening defines active c-Src-driven extracellular signaling.

CP: Cancer CP: Molecular biology PxxP motif Src tyrosine kinase TIMP2 blocking antibodies phosphoproteomic post-translational modification secretome tissue inhibitors of metalloproteinases tumor growth inhibition

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
27 06 2023
Historique:
received: 03 10 2022
revised: 07 04 2023
accepted: 03 05 2023
medline: 4 10 2023
pubmed: 27 5 2023
entrez: 27 5 2023
Statut: ppublish

Résumé

c-Src tyrosine kinase is a renowned key intracellular signaling molecule and a potential target for cancer therapy. Secreted c-Src is a recent observation, but how it contributes to extracellular phosphorylation remains elusive. Using a series of domain deletion mutants, we show that the N-proximal region of c-Src is essential for its secretion. The tissue inhibitor of metalloproteinases 2 (TIMP2) is an extracellular substrate of c-Src. Limited proteolysis-coupled mass spectrometry and mutagenesis studies verify that the Src homology 3 (SH3) domain of c-Src and the P

Identifiants

pubmed: 37243593
pii: S2211-1247(23)00550-8
doi: 10.1016/j.celrep.2023.112539
pmc: PMC10569185
mid: NIHMS1912762
pii:
doi:

Substances chimiques

Protein-Tyrosine Kinases EC 2.7.10.1
Phosphotransferases EC 2.7.-
src-Family Kinases EC 2.7.10.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112539

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM139932
Pays : United States

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Sarah J Backe (SJ)

Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

SarahBeth D Votra (SD)

Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

Matthew P Stokes (MP)

Cell Signaling Technology, Inc., Danvers, MA 01923, USA.

Endre Sebestyén (E)

The Bioinformatics CRO, Inc., Orlando, FL, USA.

Matteo Castelli (M)

Dipartimento di Chimica, Università di Pavia, 27100 Pavia, Italy.

Luca Torielli (L)

Dipartimento di Chimica, Università di Pavia, 27100 Pavia, Italy.

Giorgio Colombo (G)

Dipartimento di Chimica, Università di Pavia, 27100 Pavia, Italy.

Mark R Woodford (MR)

Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

Mehdi Mollapour (M)

Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

Dimitra Bourboulia (D)

Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY 13210, USA. Electronic address: bourmpod@upstate.edu.

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