Nerve growth factor: a protease that can activate plasminogen.

Area of Science:

• Biochemistry
• Enzymology
• Protease research

Background:

• Nerve growth factor (NGF) is primarily known for its role in neural development.
• The biochemical properties and non-neural functions of NGF are less understood.
• Mouse submandibular gland NGF is a well-characterized, stable protein preparation.

Purpose of the Study:

• To investigate the enzymatic activity of purified mouse submandibular gland nerve growth factor (NGF).
• To determine if NGF possesses protease activity against non-neural substrates.
• To elucidate the potential physiological role of NGF in biological processes beyond neurotrophism.

Main Methods:

• Purification of mouse submandibular gland NGF according to established protocols.
• Assay of NGF's ability to convert plasminogen to plasmin.
• Assessment of NGF's fibrinolytic activity in the absence of plasminogen.
• Evaluation of NGF's caseinolytic activity.
• Inhibition studies using diisopropyl fluorophosphate (DFP) to assess serine protease activity.
• Hydrolysis assays using synthetic arginine esters.

Main Results:

• Highly purified mouse submandibular gland NGF demonstrated protease activity, specifically converting plasminogen to plasmin.
• NGF exhibited no significant fibrinolytic or caseinolytic activity in the absence of plasminogen.
• Diisopropyl fluorophosphate inhibited both plasminogen activation and hydrolysis of synthetic arginine esters by NGF, indicating serine protease activity.
• Plasminogen activation was identified as the sole known non-neural substrate interaction for NGF.

Conclusions:

• Mouse submandibular gland NGF functions as a serine protease with restricted specificity.
• The identified enzymatic activity suggests a potential role for salivary NGF in activating plasminogen within the alimentary tract, potentially contributing to fibrinolysis.
• This study expands the known biological functions of NGF beyond its established neurotrophic roles.