[Natural tyrosine-kinase inhibitors]

Abstract

Changes in the degree of phosphorylation of protein tyrosine residues play a major role in the regulation of cell growth and differentiation. The biological mechanisms which control the activity of enzyme systems involved in these change (i.e. protein tyrosine-kinase [PTKs] and protein tyrosine-phosphatases) remain poorly understood. Similar to other regulation mechanisms, involving phosphorylation-dephosphorylation reactions, these enzyme systems can be regulated by naturally occurring effectors (with inhibitory or activating effects). This paper briefly reviews current knowledge on the few identified natural PTK inhibitors. The phosphoprotein PP 63 produced by rat hepatocytes inhibits insulin-receptors PTK in hepatoma cell cultures and abolishes insulin's mitogenic effect. PP 63 has a slight structural resemblance with Müllerian Inhibiting Substance, a molecule reported to inhibit epidermal growth factor (EGF) receptor PTK and to exhibit anti-mitogenic effects. Two other proteins, protein S-100 isolated from cattle brain and a thermostable factor found in human lymphoid tissues also have anti-PTK effects. Although in the current state of our knowledge, the physiologic role of these inhibitors is unclear, they may have potential value as anti-oncogenic agents as a result of their ability to decrease phosphorylation of protein tyrosine residues.