Annexin I and its Biochemical Properties

Abstract

Signal transduction triggered by ligand-receptor interaction often induces interaction of transmembrane proteins with the cytoskeletal net work at the inner surface of cell membranes. It is well known that many cytoplasmic proteins bind to phospholipid liposomes or the inner surface of plasma membranes and the interaction induces physicochemical changes in the membranes (Utsumi et al. 1981, 1982; Okimasu et al. 1982, 1986, 1987; Noboriet al. 1987). In some cases, phosphoinositides in plasma membranes are hydrolyzed and diacylglycerol (DG) is transiently produced during ligand receptor interaction (Berridge 1984). These DG and IP₃ activate proteinkinase C (PKC) (Nishizuka 1984) and increase intracellular calcium levels by releasing calcium from intracellular stores (Berridge and Irvine 1984). In this case, it has been demonstrated that DG increases the affinity of PKC for Ca²⁺ (Takai et al. 1979), and enhances the binding of the enzyme to phospholipids of plasma membranes, such as phosphatidylserine (PS), phosphatidic acid (PA), and cardiolipin (CL), by way of exposing its hydrophobic amino acid residues. No such interaction occurs with liposomes composed of uncharged phospholipids, such as phosphatidylcholine (PC) (Konig et al. 1985). Thus, the physicochemical nature of the constituent phospholipids is important for specific interaction of PKC with membranes leading to its activation: different physical forms of synthetic phospholipid vesicles or multilamellar vesicles are differentially capable of complying with the phospholipid requirement of PKC (Boni and Rando 1985). Besides PKC, other proteins such as protease (Inoue et al. 1977), actinin (Rotman et al. 1982), thrombin (Le Compte et al. 1984) and lipocortins (Sato et al. 1987) are known to be activated by interacting with phospholipids. These observations indicate that the interaction of these cytoplasmic proteins with the inner surface of plasma membranes plays a critical role in signal transduction that modulates cellular metabolism.