A novel karyopherin-beta homolog is developmentally and hormonally regulated in fetal lung

To investigate molecular mechanisms of lung organogenesis, we used represen tational difference analysis to search for glucocorticoid-inducible genes i n developing lung in a fetal rat model. Messenger RNA prepared from fetal a nd adult rat lung was used to prepare "representative amplicons," Adult-lun g complementary DNA (cDNA) amplicons were used as "driver" in successive ro unds of subtractive hybridization/amplification to isolate target fetal lun g-specific cDNAs, A single clone, which was conserved and had near-perfect homology to eight human/rodent expressed sequence tags, was used as templat e for 5' and 3' rapid amplification of cDNA ends and SPICE (system for poly merase chain reaction amplification of cDNA ends) reactions to obtain the 3 .6-kb cDNA, LGL2 (Genbank, AF 110195) encoding a deduced polypeptide (lgl2) of 963 amino acids. Northern analysis confirmed that LGL2 is differentiall y expressed in fetal lung (maximal during the pseudoglandular stage, gestat ional Days 14 to 16), induced by glucocorticoid, and enriched in epithelium relative to the mesenchyme. LGL2 was also detected in human fetal lung at gestational Week 16 as well as in human and rat fetal brain, heart, intesti ne, and kidney. We mapped LGL2 to chromosome 1p33-34.2. Comparison with seq uences in the genome database identified lgl2 as a member of the karyopheri n-beta family of nuclear import proteins, with greatest homology to transpo rtin SR. Maximal expression of LGL2 in the pseudoglandular stage of develop ment is coordinate with that of key transcription factors that regulate pro minent signal transduction pathways in fetal lung organogenesis, We propose a role for lgl2 in nuclear import of transcription factors that regulate s ignal transduction during fetal lung development.