Characterization of VIK-1: a new Vav-interacting Kruppel-like protein

Binding partners of the Src homology domains of Vav-1 were characterized by a two-hybrid screening of a Jurkat cell cDNA library. One of the isolated clones encoded a new protein named VIK that belongs to the Kruppel-like zinc-finger gene family. Genome mapping showed that a single gene positioned at chromosome 7q22.1 generated three possible isoforms containing alternative domains such as proline-rich and Kruppel-associated box A or B repressor domains. The isolated isoform, VIK-1, did not contain such motifs but presented six tandemly arranged zinc-fingers and consensus Kruppel H-C links. VIK-1 interacted both with Vav-1 and cyclin-dependent kinase 4 through two independent domains and corresponded to a Vav C-Src homology domain (SH)3 partner able to shuttle between the nucleus and the cytoplasm exhibiting functional nuclear addressing and export sequences. The results indicated a restricted expression of the protein during the G1 phase and its overexpression resulted in an inhibition of the cell-cycle progression that was reversed in the presence of Vav 1. Thus, this ubiquitous factor provides a first link between Vav-1 and the cell-cycle machinery.