Human β2 chain of laminin (formerly S chain): cDNA cloning, chromosomal localization, and expression in carcinomas

Overlapping cDNA clones that encode the full-length human laminin β2 chain, formerly called the S chain, were isolated. The cDNA of 5680 nt contains a 5391-nt open reading frame encoding 1797 amino acids. At the amino terminus is a 32-amino-acid signal peptide that is followed by the mature β2 chain polypeptide of 1765 amino acids with a calculated molecular mass of 192,389 Da. The human β2 chain is predicted to have all of the seven structural domains typical of the β chains of laminin, including the short cysteine-rich α region. The amino acid sequence of human β2 chain showed 86.1% sequence identity to the rat β2 chain, 50.0% to the human β1 chain, and 36.3% to the human β3 chain. The greatest sequence identity was in do- mains VI, V, and III. The sequence of a 24-amino-acid peptide fragment isolated from the β2 chain of laminin purified from human amniotic basement membrane matched the sequence predicted from the cDNA, confirming that the cDNA encodes human pβ2 laminin. The cDNA was used to assign the gene (LAMB2) to human chromosome 3p21 by in situ hybridization. It is not linked to genes for human laminin chains α1, β1, and γ1 or other known laminin genes. Immunostaining showed that the β2 chain is localized to the smooth muscle basement membranes of the arteries, while the homologous β1 chain is confined to the subendothelial basement membranes. The β2 chain was found in the basement membranes of ovarian carcinomas but not colon carcinomas. These results indicate that the expression of the β2 chain gene is tightly regulated in normal human tissues and in disease.