TY - JOUR T1 - The Protein Kinase A Inhibitor H89 Acts on Cell Morphology by Inhibiting Rho Kinase JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1000 LP - 1007 DO - 10.1124/jpet.300.3.1000 VL - 300 IS - 3 AU - Jost Leemhuis AU - Stephanie Boutillier AU - Gudula Schmidt AU - Dieter K. Meyer Y1 - 2002/03/01 UR - http://jpet.aspetjournals.org/content/300/3/1000.abstract N2 - The small GTPase RhoA can retract cell extensions by acting on two Rho kinases (ROCKs). Activated protein kinase A (PKA) inhibits RhoA and induces extensions. The isoquinoline H89 inhibits PKA and thus should prevent the inactivation of RhoA. In kinase assays, H89 has been recently found to inactivate a ROCK-II also. Because H89 may be able to exert opposite effects on cell extensions, we have studied the effects of H89 on neurite formation in the neuroblastoma-glioma line NG 108-15, which expresses ROCK-I and ROCK-II. We found that H89 can indeed inhibit ROCKs and PKA. Because ROCKs act downstream of RhoA, the inhibitory effect of H89 on ROCKs is most prominent. The data indicate that H89 may not be used as an antagonist of PKA in systems in which ROCKs play a role. The American Society for Pharmacology and Experimental Therapeutics ER -