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 4.9kb 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 2999nt. 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 59kDa 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.
Departments of Biology and Chemistry, Hope College, Holland, MI 49423, USA.
Ashleigh
A
Sartor
J B
JB
Kossoris
R
R
Wilcox
R
R
Shearer
A E
AE
Zeneberg
P
P
Zhao
I
I
Lazdins
Maria A
MA
Burnatowska-Hledin
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D044842:Cullin Proteins / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011817:Rabbits; D017483:Receptors, Vasopressin / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D020413:3' Untranslated Regions; D044842:Cullin Proteins; D017483:Receptors, Vasopressin