CLONING OF THE LAMA3 GENE ENCODING THE ALPHA-3-CHAIN OF THE ADHESIVE LIGAND EPILIGRIN - EXPRESSION IN WOUND REPAIR

We have isolated cDNA clones encoding the entire 170-kDa chain of epil igrin (alpha 3(Ep)) and a genomic clone encoding the alpha 3(Ep) gene (LamA3). Analysis of multiple cDNA clones revealed two distinct transc ripts (alpha 3(EpA) and alpha 3(EpB)). Sequencing of the alpha 3(EpA) transcript indicated sequence and structural homology to laminin alpha 1 and alpha 2 chains that extend from domain IIIa through the carboxy l-terminal G domain. The alpha 3(EpB) transcript encodes a larger amin o-terminal domain and contains additional epidermal growth factor repe ats and sequences corresponding to domain IV of alpha 1 laminin. Fluor escence in situ hybridization indicated that the LamA3 gene is located on chromosome 18q11.2, a locus distinct from the LamA1 gene (18p11.3) . The G domain of the epiligrin alpha 3 chain contains five subdomains that are individually related to the G subdomains reported for Drosop hila and vertebrate laminin alpha chains. Sequence divergence within t he G domain of alpha 3 epiligrin suggests that it is functionally dist inct from laminin, consistent with our previous report showing that ep iligrin interacts with different integrin adhesion receptors. Analysis of RNA from human foreskin keratinocytes (HFKs) identified multiple e piligrin transcripts that were down-regulated by viral transformation and differentiation. In contrast, epiligrin expression was up-regulate d in wound sites of human skin.