Cell
Volume 158, Issue 5, 28 August 2014, Pages 1033-1044
Journal home page for Cell

Article
A Secreted Tyrosine Kinase Acts in the Extracellular Environment

https://doi.org/10.1016/j.cell.2014.06.048Get rights and content
Under an Elsevier user license
open archive

Highlights

  • VLK is a secreted tyrosine kinase

  • VLK phosphorylates proteins in the secretory pathway and outside the cell

  • VLK is released from platelets alpha-granules in response to physiological stimuli

  • ATP coreleased with VLK during secretion supports extracellular phosphorylation

Summary

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.

Cited by (0)