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Vol. 300, Issue 3, 1000-1007, March 2002
Institut für Experimentelle und Klinische Pharmakologie und
Toxikologie, Albert-Ludwigs-Universität, Freiburg, Germany
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.
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