Identification of Targets of c-Src Tyrosine Kinase by Chemical Complementation and Phosphoproteomics

Ferrando, Isabel Martinez; Chaerkady, Raghothama; Zhong, Jun; Molina, Henrik; Jacob, Harrys K.C.; Herbst-Robinson, Katie; Dancy, Beverley M.; Katju, Vikram; Bose, Ron; Zhang, Jin; Pandey, Akhilesh; Cole, Philip A.

doi:10.1074/mcp.m111.015750

Cited by 53 publications

(63 citation statements)

References 68 publications

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“…It requires an internalization motif, 20 YTRF 23 , found in its 67-amino acid N-terminal cytoplasmic domain (8). Src can phosphorylate 20 Y of the internalization sequence (9).…”

mentioning

confidence: 99%

Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis

Chen

Donovan

Ned-Sykes

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Transferrin receptor 1 (Tfr1) facilitates cellular iron uptake through receptor-mediated endocytosis of iron-loaded transferrin. It is expressed in the intestinal epithelium but not involved in dietary iron absorption. To investigate its role, we inactivated the Tfr1 gene selectively in murine intestinal epithelial cells. The mutant mice had severe disruption of the epithelial barrier and early death. There was impaired proliferation of intestinal epithelial cell progenitors, aberrant lipid handling, increased mRNA expression of stem cell markers, and striking induction of many genes associated with epithelial-to-mesenchymal transition. Administration of parenteral iron did not improve the phenotype. Surprisingly, however, enforced expression of a mutant allele of Tfr1 that is unable to serve as a receptor for iron-loaded transferrin appeared to fully rescue most animals. Our results implicate Tfr1 in homeostatic maintenance of the intestinal epithelium, acting through a role that is independent of its iron-uptake function.transferrin receptor | intestinal epithelium | epithelial-mesenchymal transition | homeostasis | stem cell

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“…It requires an internalization motif, 20 YTRF 23 , found in its 67-amino acid N-terminal cytoplasmic domain (8). Src can phosphorylate 20 Y of the internalization sequence (9).…”

mentioning

confidence: 99%

Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis

Chen

Donovan

Ned-Sykes

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…SILAC medium was prepared as previously reported 10 . In brief, arginine- and lysine-free DMEM was supplemented with either light amino acids or heavy amino acids.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, for the non-receptor tyrosine kinases Src, v-Src and Csk, a mutant chemical rescue approach was reported and used to obtain insights into the cellular functions of these enzymes 8–10 . In this technique, a conserved active site Arg is replaced with Ala which sharply reduces catalytic activity, and this reduced activity can be complemented with the small molecule imidazole 11, 12 .…”

Section: Introductionmentioning

confidence: 99%

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

et al. 2018

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Identifying direct substrates targeted by protein kinases is important in understanding cellular physiology and intracellular signal transduction. Mass-spectrometry based quantitative proteomics provides a powerful tool for comprehensively characterizing the downstream substrates of protein kinases. This approach is efficiently applied to receptor kinases which can be precisely, directly, and rapidly activated by some agent, such as a growth factor. However, non-receptor tyrosine kinase Abl lacks the experimental advantage of extracellular growth factors as immediate and direct stimuli. To circumvent this limitation, we combine a chemical rescue approach with quantitative phosphoproteomics to identify targets of Abl and their phosphorylation sites with enhanced temporal resolution. Both known and novel putative substrates are identified, presenting opportunities for studying unanticipated functions of Abl under physiological and pathological conditions.

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“…Recently, some studies have reported that the overexpression of wild Src can promote the activity of other signaling pathway molecules (Elsberger et al, 2010;Yasmeen et al, 2010). In fact, Src kinase has been proven to be able to react with a variety of proteins, including receptor tyrosine kinase-colony-stimulating factor receptor-1, plateletderived growth factor receptor, vascular endothelial growth factor receptor, human epidermal growth factor receptor-2, and human epidermal growth factor receptor-3 (Ferrando et al, 2012;Nagaraj et al, 2013). Other acting factors include signal transduction and transcription activation factors, heterotrimeric G protein, mitogen-activated protein kinase (MAPK), cyclin D and E, and focal adhesion kinase (Khoury et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Activation of Src tyrosine kinase in esophageal carcinoma cells in different regulatory environments and corresponding occurrence mechanism

Song

Gan

et al. 2016

Genet. Mol. Res.

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ABSTRACT. This study aims at observing the expression of activated Src tyrosine kinase in esophageal squamous cell carcinoma (ESCC), and exploring the relationship of Src tyrosine kinase with the occurrence and progression of ESCC. Immunohistochemistry, immunofluorescence, and immunoblotting are employed to investigate the expression of Src tyrosine kinase in the ESCC tissue. Cellular immunofluorescence is used to measure the expression of activated Src tyrosine kinase in TE1 and TE9 cell lines of human ESCC tissues and EPC1-htert and EPC2-htert cell lines of esophageal epithelial cells. Src tyrosine kinase is overexpressed in ESCC tissue and underexpressed in normal esophageal mucosa. Furthermore, it is overexpressed in the TE1 and TE9 cell lines of human ESCC tissue and underexpressed in the EPC1-htert and EPC2-htert cell lines of esophageal epithelial cells. Src tyrosine kinase shows a higher expression in human ESCC tissue than in normal esophageal mucosa. The difference is statistically significant (P < 0.05). The activation of Src tyrosine kinase plays an important role in the occurrence and development of ESCC.

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Identification of Targets of c-Src Tyrosine Kinase by Chemical Complementation and Phosphoproteomics

Cited by 53 publications

References 68 publications

Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis

Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

Activation of Src tyrosine kinase in esophageal carcinoma cells in different regulatory environments and corresponding occurrence mechanism

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