Receptor tyrosine kinase (RTK) mediated tyrosine phosphor-proteome from Drosophila S2 (ErbB1) cells reveals novel signaling networks.
Protein phosphorylation mediates many critical cellular responses and is essential for many biological functions during development. About one-third of cellular proteins are phosphorylated, representing the phosphor-proteome, and phosphorylation can alter a protein's function, activity, localization and stability. Tyrosine phosphorylation events mediated by aberrant activation of Receptor Tyrosine Kinase (RTK) pathways have been proven to be involved in the development of several diseases including cancer. To understand the systems biology of RTK activation, we have developed a phosphor-proteome focused on tyrosine phosphorylation events under insulin and EGF signaling pathways using the PhosphoScan technique coupled with high-throughput mass spectrometry analysis. Comparative proteomic analyses of all these tyrosine phosphorylation events revealed that around 70% of these pY events are conserved in human orthologs and paralogs. A careful analysis of published in vivo tyrosine phosphorylation events from literature and patents revealed that around 38% of pY events from Drosophila proteins conserved on 185 human proteins are confirmed in vivo tyrosine phosphorylation events. Hence the data are validated partially based on available reports, and the credibility of the remaining 62% of novel conserved sites that are unpublished so far is very high but requires further follow-up studies. The novel pY events found in this study that are conserved on human proteins could potentially lead to the discovery of drug targets and biomarkers for the detection of various cancers and neurodegenerative diseases.
Krishnamoorthy
Srinivasan
S
Department of Surgery, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. ksrini10@gmail.com
D000818:Animals; D017124:Conserved Sequence; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D009369:Neoplasms / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics; D010748:Phosphopeptides / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020543:Proteome; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013045:Species Specificity
D029721:Drosophila Proteins; D007328:Insulin; D010748:Phosphopeptides; D010750:Phosphoproteins; D020543:Proteome; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases