Connective tissue growth factor (CTGF) is a member of a protein family in which 38 cysteine residues are conserved. Although a wide variety of important biological functions have been ascribed to these proteins in recent years, the regulation of their gene expression for most members is virtually unknown, We studied the effects of protein kinase C (PKC) and tyrosine kinase on the expression of CTGF and observed that at the mRNA level CTGF expression is inhibited by the activation of PKC, but stimulated by the inhibition of PKC and tyrosine kinase. We further determined that the novel and the classical PKC isoforms are needed for the inhibition, but the atypical isoforms are not involved. Our data suggest that phosphorylation on serine/threonine and tyrosine by PKC and by tyrosine kinase are all inhibitory to the expression of CTGF.