A secreted tyrosine kinase acts in the extracellular environment.

Article Details

Citation

Bordoli MR, Yum J, Breitkopf SB, Thon JN, Italiano JE Jr, Xiao J, Worby C, Wong SK, Lin G, Edenius M, Keller TL, Asara JM, Dixon JE, Yeo CY, Whitman M

A secreted tyrosine kinase acts in the extracellular environment.

Cell. 2014 Aug 28;158(5):1033-44. doi: 10.1016/j.cell.2014.06.048.

PubMed ID
25171405 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Interstitial collagenaseP03956Details
Collagenase 3P45452Details
Laminin subunit alpha-1P25391Details
Matrix metalloproteinase-14P50281Details
Matrix metalloproteinase-19Q99542Details