Title |
A Secreted Tyrosine Kinase Acts in the Extracellular Environment
|
---|---|
Published in |
Cell, August 2014
|
DOI | 10.1016/j.cell.2014.06.048 |
Pubmed ID | |
Authors |
Mattia R. Bordoli, Jina Yum, Susanne B. Breitkopf, Jonathan N. Thon, Joseph E. Italiano, Junyu Xiao, Carolyn Worby, Swee-Kee Wong, Grace Lin, Maja Edenius, Tracy L. Keller, John M. Asara, Jack E. Dixon, Chang-Yeol Yeo, Malcolm Whitman |
Abstract |
Although tyrosine phosphorylation of extracellular proteins has been reported to occur extensively in vivo, no secreted protein tyrosine kinase has been identified. As a result, investigation of the potential role of extracellular tyrosine phosphorylation in physiological and pathological tissue regulation has not been possible. Here, we show that VLK, a putative protein kinase previously shown to be essential in embryonic development, is a secreted protein kinase, with preference for tyrosine, that phosphorylates a broad range of secreted and ER-resident substrate proteins. We find that VLK is rapidly and quantitatively secreted from platelets in response to stimuli and can tyrosine phosphorylate coreleased proteins utilizing endogenous as well as exogenous ATP sources. We propose that discovery of VLK activity provides an explanation for the extensive and conserved pattern of extracellular tyrosine phosphophorylation seen in vivo, and extends the importance of regulated tyrosine phosphorylation into the extracellular environment. |
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Geographical breakdown
Country | Count | As % |
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United States | 4 | 31% |
United Kingdom | 3 | 23% |
Switzerland | 1 | 8% |
Unknown | 5 | 38% |
Demographic breakdown
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Members of the public | 8 | 62% |
Scientists | 5 | 38% |
Mendeley readers
Geographical breakdown
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Finland | 2 | 1% |
United States | 2 | 1% |
Hungary | 1 | <1% |
United Kingdom | 1 | <1% |
Chile | 1 | <1% |
Japan | 1 | <1% |
China | 1 | <1% |
Unknown | 167 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 47 | 27% |
Researcher | 38 | 22% |
Student > Master | 15 | 9% |
Student > Bachelor | 14 | 8% |
Professor | 12 | 7% |
Other | 29 | 16% |
Unknown | 21 | 12% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 62 | 35% |
Biochemistry, Genetics and Molecular Biology | 52 | 30% |
Medicine and Dentistry | 10 | 6% |
Neuroscience | 6 | 3% |
Engineering | 5 | 3% |
Other | 15 | 9% |
Unknown | 26 | 15% |