SUBCELLULAR-LOCALIZATION AND PROTEIN-INTERACTION OF THE HUMAN LIMK2 GENE EXPRESSING ALTERNATIVE TRANSCRIPTS WITH TISSUE-SPECIFIC REGULATION

In our efforts to explore possible roles of proteins with a LIM domain , which is a cysteine-rich Zinc-binding motif, in differentiation and oncogenesis in the lung, we have cloned a human LIMK2 gene and identif ied two alternative transcripts, LIMK2a and LIMK2b, which are probably due to variation in transcriptional initiation. The former encodes a protein containing two LIM domains, a PDZ domain, and a kinase domain, while the latter has only one and half LIM domains. The predominance of the two transcripts appears to be regulated in a tissue-specific ma nner. Alteration of the regulation is also observed in some cancer cel l lines. Transfection studies have shown an association of 63-kDa and 58-kDa proteins with the LIMK2a and LIMK2b protein; the former is dist ributed in the cytoplasm and nucleus and the latter occurs mainly in t he cytoplasm and is scarcely translocated to the nucleus. In contrast, a truncated LIMK2-Kinase has a nuclear location, not showing the prot ein association. (C) 1996 Academic Press, Inc.