Multiple forms of phosphoinositide-specific phospholipase C and different modes of activation.

Phosphoinositide-specific phospholipase C (PLC) plays a crucial role in initiating the surface-mediated signal transduction by generating second messenger molecules, diacylglycerol, and inositol phosphates (see [ 1-41 for reviews). Results accumulated during the last few years clearly indicate that the response of phosphoinositide signalling to a specific stimulus varies depending on tissue and cell types, even when the tissues and cells contain an identical subtype receptor. The simplest explanation for the heterogeneous response is that the post-receptor components, G-protein and PLC, required for the phosphoinositide signalling are differently expressed in different cells. It is noteworthy that at least two types of G-proteins, pertussin-toxin-sensitive and -insensitive forms are involved in phosphoinositide signalling [5, 61 and that, as discussed below, a number of PLC isoforms exist in mammalian tissues. There are three possible patterns of coupling for a receptor to the post-receptor components. First, a receptor might couple to a unique G-protein which then interacts with multiple PLC enzymes. Secondly, a receptor might couple to a variety of G-proteins which are then faithfully coupled to a single PLC. Thirdly, a receptor might couple to a variety of PLC forms through several different G-proteins. Information available at the present time cannot differentiate one from the other. A number of distinct PLCs have been purified from a variety of mammalian tissues [7] and several forms have been molecularly cloned and sequenced. Comparison of their deduced amino acid sequences and immunological cross-reactivity indicates that mammalian PLC can be divided into four types: PLC-a, PLC-B, PLC-y and PLC-6, which are discrete gene products. All four forms are single polypeptide enzymes. Molecular masses measured by SDS/PAGE are 62-68 kDa for PLC-