New insights into the families of PLC enzymes: looking back and going forward

A study in this issue of the Biochemical Journal by Harden and colleagues, in association with one published in the Biochemical Journal very recently [Hwang, Oh, Shin, Kim, Ryu and Suh (2005) Biochem. J. 389, 181–186], have defined a new member of the superfamily of PLC (phosphoinositide-specific phospholipase C) enzymes, PLCη. Two isoforms, PLCη1 and PLCη2, and their splice variants add to the molecular diversity of PLC enzymes. The studies of PLCη regulation suggest that at least some splice variants of PLCη2 could be regulated by the G-protein subunits Gβγ. As two other families, PLCβ and PLCϵ, are also regulated through heterotrimeric G-proteins, this finding reveals further complexity and possible interplay between different PLC families and their regulatory networks. At this point, when it is likely that the PLCη family completes the effort of identifying new members of this related group of PLC enzymes, I also discuss some more general concepts of PLC regulation and catalysis, and challenges awaiting their further studies.