Background: The PKC1 gene of Saccharomyces cerevisiae encodes a homologue of mammalian protein kinase C (PKC) that is required for yeast cell growth. Pkc1 has been proposed to regulate a protein kinase cascade which includes the Bck1, Mkk1/Mkk2 and Mpk1 kinases. The functional relationship between Pkc1 and mammalian PKCs is unknown. Another signal transduction in Saccharomyces cerevisiae, the mating pheromone signalling pathway, is mediated by a heterotrimeric G protein, and causes cell cycle arrest in the G1 interval. It is not clear whether PKC is involved in this pathway. The effects of overexpression of PKCs in mammalian cells have been widely studied to analyse the function of PKCs in vivo.Results: We isolated a human cDNA which encodes a protein kinase C type η (PKC‐η) by complementation of pkc1 mutations in Saccharomyces cerevisiae. The human PKC‐η was able to complement the growth defect caused by the deletion of PKC1, whereas PKC‐η was unable to suppress the defect caused by deletion of BCK1. We also isolated human cDNAs that can suppress the adaptation defect of sst2. One of them encodes a protein kinase C type δ (PKC‐δ). Expression of this gene in yeast stimulated an adaptation to the pheromone response. Human PKC‐δ suppressed the adaptation defect of a pheromone receptor mutation lacking its C‐terminal domain, but not that of a G protein β‐subunit mutation eliminating signal‐induced phosphorylation, and not the lethality of the gpa1 null mutation. Moreover, overexpression of PKC‐η in NIH3T3 cells induced anchorage‐independent growth.Conclusions: PKC‐η has a biological activity which is closely related to Pkc1, and PKC‐η activates the Pkc1‐mediated pathway through an activation of the Bck1 kinase that is a homologue of MAP kinase kinase kinase. PKC‐η appears to play a critical role in growth control of yeast and mammalian cells. Suppression experiments with PKC‐δ suggest that PKC‐δ desensitizes the pathway by regulating an aspect of G protein function.