Protein kinase C and annexins: Unusual calcium response elements in the cell

Protein kinase C and the annexins appear to share some unusual and potentially important membrane -and calcium-binding properties. While these proteins are calcium response elements, they are not calcium-binding proteins in the formal sense; at intracellular calcium concentrations, they only bind significant amounts of calcium when membranes or other suitable surfaces are present. The number of calcium ions bound per protein is large (> 8) and this stoichiometry, at the protein-membrane interface, may provide the large number of contact points needed for the very high-affinity interaction that is observed. The further ability of annexins and PKC to form structures with properties of integral membrane proteins may be important to provide a type of long-term cell signalling that produces a contitutively active kinase or ion channel activity. Selectivity for phospholipids in bilayer form is modest with respect to the acidic phospholipids but there is a surprising preference for phosphatidylethanomaline as the neutral phospholipid matrix. Along with other unusual properties, these proteins offer the potential for unique types of cell regulation events.