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Proteome Sci. 2018 Aug 18;16:16. doi: 10.1186/s12953-018-0143-7. eCollection 2018.

Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates.

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1Department of Biochemistry, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5 Canada.
2Computational Biology Program, Ontario Institute for Cancer Research, 661 University Ave Suite 510, Toronto, ON M5G 0A3 Canada.
3Department of Medical Biophysics, University of Toronto, 101 College Street Suite 15-701, Toronto, ON M5G 1L7 Canada.
4Department of Pathology, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5 Canada.
5Saskatchewan Cancer Agency, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5 Canada.
6Department of Molecular Biophysics and Biochemistry and MS & Proteomics Resource, WM Keck Foundation Biotechnology Resource Laboratory, Yale University, New Haven, CT USA.



The non-receptor tyrosine kinase, SRMS (Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites) is a member of the BRK family kinases (BFKs) which represents an evolutionarily conserved relative of the Src family kinases (SFKs). Tyrosine kinases are known to regulate a number of cellular processes and pathways via phosphorylating substrate proteins directly and/or by partaking in signaling cross-talks leading to the indirect modulation of various signaling intermediates. In a previous study, we profiled the tyrosine-phosphoproteome of SRMS and identified multiple candidate substrates of the kinase. The broader cellular signaling intermediates of SRMS are unknown.


In order to uncover the broader SRMS-regulated phosphoproteome and identify the SRMS-regulated indirect signaling intermediates, we performed label-free global phosphoproteomics analysis on cells expressing wild-type SRMS. Using computational database searching and bioinformatics analyses we characterized the dataset.


Our analyses identified 60 hyperphosphorylated (phosphoserine/phosphothreonine) proteins mapped from 140 hyperphosphorylated peptides. Bioinfomatics analyses identified a number of significantly enriched biological and cellular processes among which DNA repair pathways were found to be upregulated while apoptotic pathways were found to be downregulated. Analyses of motifs derived from the upregulated phosphosites identified Casein kinase 2 alpha (CK2α) as one of the major potential kinases contributing to the SRMS-dependent indirect regulation of signaling intermediates.


Overall, our phosphoproteomics analyses identified serine/threonine phosphorylation dynamics as important secondary events of the SRMS-regulated phosphoproteome with implications in the regulation of cellular and biological processes.


BRK; FRK; Mass spectrometry; Non-receptor tyrosine kinase; PTK5; PTK6; PTK70; Phosphoproteomics; SRMS; Src

Conflict of interest statement

Not applicableNot applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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