GENGHIS KHAN (GEK) AS A PUTATIVE EFFECTOR FOR DROSOPHILA CDC42 AND REGULATOR OF ACTIN POLYMERIZATION

The small GTPases Cdc42 and Rac regulate a variety of biological proce sses, including actin polymerization, cell proliferation, and JNK/mito gen-activated protein kinase activation, conceivably via distinct effe cters, Whereas the effector for mitogen-activated protein kinase activ ation appears to be p65(PAK), the identity of effector(s) for actin po lymerization remains unclear, We have found a putative effector for Dr osophila Cdc42, Genghis Khan (Gek), which binds to Dcdc42 in a GTP-dep endent and effector domain-dependent manner, Gek contains a predicted serine/threonine kinase catalytic domain that is 63% identical to huma n myotonic dystrophy protein kinase and has protein kinase activities. It also possesses a large coiled-coil domain, a putative phorbol este r binding domain, a pleckstrin homology domain, and a Cdc42 binding co nsensus sequence that is required for its binding to Dcdc42, To study the in vivo function of gek, we generated mutations in the Drosophila gek locus, Egg chambers homozygous for gek mutations exhibit abnormal accumulation of F-actin and are defective in producing fertilized eggs , These phenotypes can be rescued by a wild-type gek transgene, Our re sults suggest that this multidomain protein kinase is an effector for the regulation of actin polymerization by Cdc42.