Matriptase

Matriptase is a type of serine protease that plays a crucial role in various biological processes, including epithelial development, hair follicle growth, and immune system functioning. It is encoded by the ST14 gene in humans. Matriptase is known for its involvement in the processing of other proteins, contributing to cellular activities such as signaling, proliferation, and migration. Its activity is tightly regulated within the body, as dysregulation can lead to pathological conditions, including cancer, skin diseases, and certain inflammatory disorders.

Structure

Matriptase is a complex enzyme composed of several domains: a catalytic domain typical of serine proteases, a SEA domain (sea urchin sperm protein, enterokinase, and agrin), four CUB domains (complement C1r/C1s, Uegf, Bmp1), and three LDLRA domains (low-density lipoprotein receptor class A). This structure is essential for its function and regulation, allowing it to interact with various substrates and inhibitors.

Function

The primary function of matriptase is to cleave peptide bonds in protein substrates, a process critical for the activation of many physiological pathways. It is involved in the activation of urokinase and hepatocyte growth factor (HGF), which are important for cell migration and proliferation. Matriptase also plays a role in the degradation of the extracellular matrix, a key event in cancer metastasis.

Regulation

Matriptase activity is regulated by its endogenous inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1). The balance between matriptase and HAI-1 is crucial for maintaining physiological homeostasis. Dysregulation of this balance can lead to excessive proteolytic activity, contributing to the progression of various diseases.

Clinical Significance

1. 1. 1. Cancer

Overexpression of matriptase has been observed in several types of cancer, including breast, ovarian, and prostate cancer. Its role in tumor progression and metastasis makes it a potential target for cancer therapy.

1. 1. 1. Skin Diseases

Mutations in the ST14 gene, leading to matriptase deficiency, have been linked to autosomal recessive ichthyosis with hypotrichosis syndrome, a condition characterized by severe skin scaling and hair loss.

1. 1. 1. Inflammatory Disorders

Matriptase may also be involved in inflammatory processes, although the exact mechanisms and implications of its activity in such conditions are still under investigation.

Research Directions

Current research on matriptase focuses on understanding its precise biological functions, regulatory mechanisms, and potential as a therapeutic target. Inhibitors of matriptase are being explored for their therapeutic potential in cancer and other diseases associated with its dysregulation.

See Also

• Serine protease inhibitors
• Protease-activated receptors
• Cancer therapy