CHARACTERIZATION OF THE MADH2 SMAD2 GENE, A HUMAN MAD HOMOLOG RESPONSIBLE FOR THE TRANSFORMING-GROWTH-FACTOR-BETA AND ACTIVIN SIGNAL-TRANSDUCTION PATHWAY/
S. Takenoshita et al., CHARACTERIZATION OF THE MADH2 SMAD2 GENE, A HUMAN MAD HOMOLOG RESPONSIBLE FOR THE TRANSFORMING-GROWTH-FACTOR-BETA AND ACTIVIN SIGNAL-TRANSDUCTION PATHWAY/, Genomics, 48(1), 1998, pp. 1-11
The transforming growth factor beta (TGF-beta) super-family is a famil
y of multifunctional cytokines that transduce signals via serine/threo
nine kinase receptors. Recent studies revealed that Mothers against dp
p (Mad) in Drosophila and its homologs play important roles in the int
racellular signal transduction of the serine/threonine kinase receptor
s. In mammals, one of the Mad homologs, MADH2 (also termed Smad2), was
reported to be a mediator of TGF-beta and activin signaling and was f
ound mutated in some of the colon and lung cancer cases. We describe h
ere the genomic organization of the human MADH2 gene. The gene is comp
osed of 12 exons; 2 exons 1, i.e., exon 1a and 1b, are used separately
or in conjunction to form exon 1a-exon 1b-exon 2 alternatively splice
d mRNA. The 2 exons 1 are closely located, and the MADH2 mRNAs are tra
nscribed from two promoters in one CpG island. The promoter activity i
n the 5' upstream sequence was confirmed by the luciferase assay. The
3' end of the mRNA is heterogenous, and we found several polyadenylati
on signals. Northern blot analysis revealed high expression of the MAD
H2 mRNA, e.g., in skeletal muscle, heart, and placenta. RT-PCR assay u
sing primers in exons 2 and 4 and direct nucleotide sequencing proved
that exon 3 is spliced out in about 10% of MADH2 in human placenta. Th
ese data will be valuable for studying the MADH2 function in both norm
al cells and cancer cells. (C) 1998 Academic Press.