A secreted tyrosine kinase acts in the extracellular environment.

Cell 2014 Aug;158(5):1033-1044

Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2014.06.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149754PMC
August 2014
43 Reads

Publication Analysis

Top Keywords

tyrosine phosphorylation
12
protein kinase
8
phosphorylation extracellular
8
extracellular tyrosine
8
secreted protein
8
extracellular environment
8
tyrosine kinase
8
tyrosine
7
secreted
5
extracellular
5
find vlk
4
response stimuli
4
proteins find
4
vlk rapidly
4
rapidly quantitatively
4
secreted platelets
4
quantitatively secreted
4
substrate proteins
4
platelets response
4
broad range
4

Similar Publications