Truncated form of VACM-1/cul-5 with an extended 3′ untranslated region stimulates cell growth via a MAPK-dependent pathway

We have sequenced a 4.9 kb clone (KLB22) which shares 99% sequence homology with the rabbit vasopressin-activated calcium mobilizing (VACM-1) protein. The 5′ terminus sequence of KLB22 cDNA (nucleotides 1–1961) is continuous and overlapping with nucleotides 1226–3186 of the VACM-1 cDNA sequence. The 3′UTR of KLB22 cDNA extends beyond the 3′UTR of VACM-1 by 2999 nt. KLB22 cDNA encodes a 497 amino acid protein, which putatively begins at Met 284 of the 780 amino acid VACM-1 protein. The in vitro translation of KLB22 cDNA yields a 59 kDa protein. When expressed in cos-1 cells, the truncated VACM-1 protein localizes to the nucleus. KLB22 cDNA transfected cells show increased growth rates and increased levels of phosphorylated MAPK when compared to the vector or to VACM-1 cDNA transfected cells. Finally, in vivo, KLB22 protein expression is tissue specific and can be detected in kidney and in heart atrium. These results suggest that truncated VACM-1 cDNA (KLB22) increases cell proliferation through a MAPK pathway.