In human placenta membranes the rate limiting enzyme for PIP 2 formation from PI is PIP kinase. GTPγS is shown to activate PIP kinase by increasing V m a x of the enzyme. It is suggested that a guanine nucleotide regulatory protein is involved in the activation of PIP kinase although coupling with a specific receptor is not yet known. Since PIP 2 is the preferred substrate of phospholipase C, the possibility exists that an increase of PIP 2 due to activation of PIP kinase leads to an enhancement of phospholipase C activity and hence to an increased production of IP 3 and DAG.