Biochemistry, regulation and potential function of kallistatin.
Components of the tissue kallikrein-kinin system include tissue kallikrein, kallistatin (kallikrein-binding protein), kininogen, kinin, bradykinin B1 and B2 receptors, and kininases. Tissue kallikrein is a serine proteinase which is capable of cleaving kininogen substrate to release the vasoactive kinin peptide. The binding of kinin to its specific receptor at target organs can produce a wide spectrum of biological effects. Kinin generation is primarily determined by the activity and availability of kallikrein since the level of kininogen is not a rate-limiting factor. Kallikrein levels are controlled by its rate of synthesis, activation, inactivation and clearance. The synthesis of tissue kallikrein is regulated transcriptionally, and its activity is regulated through post-translational processing and inactivation by inhibitors. Kallistatin is a newly discovered serine proteinase inhibitor (serpin) which forms a specific and covalently-linked complex with tissue kallikrein. Kallistatin may regulate tissue kallikrein's activity, bioavailability and clearance rate at the post-translational level. The major site of kallistatin synthesis is the liver with lower expression levels in the pancreas and kidney. Unlike many other serpins which are only present in the plasma, kallistatin is found in various tissues, cells and bodily fluids. The fact that both tissue kallikrein and kallistatin are widely distributed in tissues suggests kallistatin's role as a potential regulator of kallikrein outside the circulation. Protein purification and molecular cloning techniques have been used to study the structure, regulation and function of the components of the kallikrein-kinin system and for exploring their roles in ion transport, inflammation and blood pressure regulation. Considerable progress has been made in recent years to achieve these goals. This article provides an overview of the biochemical properties and potential physiological and pathophysiological roles of kallistatin.
Chao
J
J
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
Chao
L
L
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D015843:Serpins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D002352:Carrier Proteins; D015843:Serpins; C051324:kallistatin