STIMULATION OF CELL ELONGATION IN TELEOST ROD PHOTORECEPTORS BY DISTINCT PROTEIN-KINASE INHIBITORS

The rod photoreceptors of teleost retinas elongate in the light. To ch aracterize the role of protein kinases in elongation, pharmacological studies were carried out with rod fragments consisting of the motile i nner segment and photosensory outer segment (RIS-ROS), Isolated RIS-RO S were cultured in the presence of membrane-permeant inhibitors that e xhibit selective activity toward specific serine/threonine protein kin ases. We report that three distinct classes of protein kinase inhibito rs stimulated elongation in darkness: (1) cyclic AMP-dependent protein kinase (PKA)-selective inhibitors (H-89 and KT5720), (2) a protein ki nase C (PKC)-selective inhibitor (GF 109203X) that affects most PKC is oforms, and (3) a kinase inhibitor (H-85) that does not affect PKC and PKA in vitro. Other kinase inhibitors tested neither stimulated elong ation in darkness nor inhibited light-induced elongation; these includ e the myosin light chain kinase inhibitors ML-7 and ML-9, the calcium- calmodulin kinase II inhibitor KN-62, and inhibitors or activators of diacylglycerol-dependent PKCs (sphingosine, calphostin C, chelerythrin e, and phorbol esters),The myosin light chain kinase inhibitors as wel l as the PKA and PKC inhibitors H-89 and GF 109203X all enhanced light -induced elongation, These observations suggest that light-induced RIS -ROS elongation is inhibited by both PKA and an unidentified kinase or kinases, possibly a diacylglycerol-independent form of PKC.