Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates
Abstract Background 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 kin...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-08-01
|
| Series: | Proteome Science |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12953-018-0143-7 |
| _version_ | 1828779646129274880 |
|---|---|
| author | Raghuveera Kumar Goel Mona Meyer Marta Paczkowska Jüri Reimand Frederick Vizeacoumar Franco Vizeacoumar TuKiet T. Lam Kiven Erique Lukong |
| author_facet | Raghuveera Kumar Goel Mona Meyer Marta Paczkowska Jüri Reimand Frederick Vizeacoumar Franco Vizeacoumar TuKiet T. Lam Kiven Erique Lukong |
| author_sort | Raghuveera Kumar Goel |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-12-11T17:06:07Z |
| format | Article |
| id | doaj.art-0388ac128d2f4b62a7a03254eb18cf4f |
| institution | Directory Open Access Journal |
| issn | 1477-5956 |
| language | English |
| last_indexed | 2024-12-11T17:06:07Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Proteome Science |
| spelling | doaj.art-0388ac128d2f4b62a7a03254eb18cf4f2022-12-22T00:57:41ZengBMCProteome Science1477-59562018-08-0116111410.1186/s12953-018-0143-7Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediatesRaghuveera Kumar Goel0Mona Meyer1Marta Paczkowska2Jüri Reimand3Frederick Vizeacoumar4Franco Vizeacoumar5TuKiet T. Lam6Kiven Erique Lukong7Department of Biochemistry, College of Medicine, University of SaskatchewanComputational Biology Program, Ontario Institute for Cancer ResearchComputational Biology Program, Ontario Institute for Cancer ResearchComputational Biology Program, Ontario Institute for Cancer ResearchDepartment of Pathology, Cancer Cluster, College of Medicine, University of SaskatchewanDepartment of Pathology, Cancer Cluster, College of Medicine, University of SaskatchewanDepartment of Molecular Biophysics and Biochemistry and MS & Proteomics Resource, WM Keck Foundation Biotechnology Resource Laboratory, Yale UniversityDepartment of Biochemistry, College of Medicine, University of SaskatchewanAbstract Background 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. Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12953-018-0143-7SRMSPTK70SrcBRKFRKPTK6 |
| spellingShingle | Raghuveera Kumar Goel Mona Meyer Marta Paczkowska Jüri Reimand Frederick Vizeacoumar Franco Vizeacoumar TuKiet T. Lam Kiven Erique Lukong Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates Proteome Science SRMS PTK70 Src BRK FRK PTK6 |
| title | Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates |
| title_full | Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates |
| title_fullStr | Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates |
| title_full_unstemmed | Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates |
| title_short | Global phosphoproteomic analysis identifies SRMS-regulated secondary signaling intermediates |
| title_sort | global phosphoproteomic analysis identifies srms regulated secondary signaling intermediates |
| topic | SRMS PTK70 Src BRK FRK PTK6 |
| url | http://link.springer.com/article/10.1186/s12953-018-0143-7 |
| work_keys_str_mv | AT raghuveerakumargoel globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates AT monameyer globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates AT martapaczkowska globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates AT jurireimand globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates AT frederickvizeacoumar globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates AT francovizeacoumar globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates AT tukiettlam globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates AT kiveneriquelukong globalphosphoproteomicanalysisidentifiessrmsregulatedsecondarysignalingintermediates |