Up-regulation of p21- and RhoA-activated protein kinases in human pregnant myometrium.
The role of small ras homologous GTP-binding proteins in the regulation of smooth muscle contractility has become increasingly apparent but there is still little information about the presence of these proteins in human uterine smooth muscle. Messenger RNAs for p21-activated protein kinase isoforms (PAK1, PAK2, and PAK3) were detectable in both nonpregnant and pregnant human myometrial tissue. However, PAK3 protein was not detectable and the proteins for PAK1 and PAK2 were only detectable in pregnant tissue. Moreover there was a large increase in the constitutively active p34 protein fragment of PAK2 in pregnant tissue. Protein expression of RhoA-activated protein kinases 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. Preincubation of the tissue with C3 toxin inhibited LPA-stimulated MLC20 phosphorylation and lowered the basal phosphorylation level of MLC20. Thus ROKS and PAKS have the potential to regulate uterine contractility and/or load-bearing during human pregnancy.
Moore
F
F
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom.
Da Silva
C
C
Wilde
J I
JI
Smarason
A
A
Watson
S P
SP
López Bernal
A
A
D036002:ADP Ribose Transferases / Q000494:pharmacology; D001905:Botulinum Toxins; D003014:Clostridium botulinum / Q000378:metabolism; D005260:Female; D006801:Humans; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology*; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D011494:Protein Kinases / Q000378:metabolism*; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011494:Protein Kinases; D001905:Botulinum Toxins; D015689:Oncogene Protein p21(ras); D020742:rhoA GTP-Binding Protein