Up-regulation of p21-and RhoA-activated protein kinases in human pregnant myometrium

The role of small res homologous GTP-binding proteins in the regulation of smooth muscle contractility has become increasingly apparent but there is s till little information about the presence of these proteins in human uteri ne smooth muscle. Messenger RNAs for pal-activated protein kinase isoforms (PAK1, PAK2, and PAK3) were detectable in both nonpregnant and pregnant hum an myometrial tissue. However, PAK3 protein was not detectable and the prot eins for PAK1 and PAK2 were only detectable in pregnant tissue. Moreover th ere was a large increase in the constitutively active p34 protein fragment of PAK2 in pregnant tissue. Protein expression of RhoA-activated protein ki nases isoforms (ROK1 and ROK2) also increased during pregnancy. Stimulation of RhoA signaling in pregnant myometrial tissue with lysophosphatic acid ( LPA) increased the level of myosin light chain (MLC20) phosphorylation. Pre incubation of the tissue with C3 toxin inhibited LPA-stimulated MLC20 phosp horylation and lowered the basal phosphorylation level of MLC20. Thus ROKS and PAKS have the potential to regulate uterine contractility and/or load-b earing during human pregnancy. (C) 2000 Academic Press.