A secreted tyrosine kinase acts in the extracellular environment

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• Extensive in vivo tyrosine phosphorylation of extracellular proteins is observed, but the responsible secreted protein tyrosine kinases remain unidentified.
• The lack of identified secreted protein tyrosine kinases has hindered research into extracellular tyrosine phosphorylation's role in tissue regulation.

Purpose of the Study:

• To identify a secreted protein tyrosine kinase responsible for extracellular protein phosphorylation.
• To investigate the function and substrates of the identified kinase in the extracellular environment.

Main Methods:

• Utilized biochemical assays to characterize the kinase activity of Vascular Like Kinase (VLK).
• Investigated the secretion of VLK from platelets upon stimulation.
• Assessed the substrate specificity of VLK for secreted and ER-resident proteins.
• Examined the role of ATP sources in VLK-mediated phosphorylation.

Main Results:

• Vascular Like Kinase (VLK) was identified as a secreted protein tyrosine kinase.
• VLK phosphorylates a diverse array of secreted and ER-resident substrate proteins.
• VLK is rapidly and quantitatively secreted from platelets in response to stimuli.
• VLK can phosphorylate proteins using both endogenous and exogenous ATP.

Conclusions:

• The discovery of VLK provides a molecular basis for the widespread in vivo extracellular tyrosine phosphorylation.
• VLK extends the significance of regulated tyrosine phosphorylation into the extracellular milieu.
• VLK is crucial for understanding physiological and pathological tissue regulation via extracellular signaling.