The kinesin-like motor protein KIF1C occurs in intact cells as a dimer andassociates with proteins of the 14-3-3 family

Proteins of the kinesin superfamily are regulated in their motor activity a s well as in their ability to bind to their cargo by carboxyl-terminal asso ciating proteins and phosphorylation. KIF1C, a recently identified member o f the KIF1/Unc104 family, was shown to be involved in the retrograde vesicl e transport from the Golgi-apparatus to the endoplasmic reticulum. In a yea st two-hybrid screen using the carboxyl-terminal 350 amino acids of KIF1C a s a bait, we identified as binding proteins 14-3-3 beta, gamma, epsilon, an d zeta. In addition, a clone encoding the carboxyl-terminal 290 amino acids of KIF1C was found, indicating a potential for KIF1C to dimerize. Subseque nt transient overexpression experiments showed that KIF1C can dimerize effi ciently. However, in untransfected cells, only a small portion of KIF1C was detected as a dimer. The association of 14-3-3 proteins with KIF1C could b e confirmed in transient expression systems and in untransfected cells and was dependent on the phosphorylation of serine 1092 located in a consensus binding sequence for 14-3-3 ligands. Serine 1092 was a substrate for the pr otein kinase casein kinase II in vitro, and inhibition of casein kinase II in cells diminished the association of KIF1C with 14-3-3 gamma. Our data th us suggest that KIF1C can form dimers and is associated with proteins of th e 14-3-3 family.