Structure of the gene encoding the human leukocyte adhesion molecule-1 (TQ1, Leu-8) of lymphocytes and neutrophils

Abstract

The leukocyte adhesion molecule-1 (LAM-1, TQ1, Leu-8), expressed by human lymphocytes, neutrophils, monocytes, and their precursors, is a member of the selectin family of cellular adhesion/homing receptors which play important roles in leukocyte-endothelial cell interactions. These cell surface molecules contain an amino-terminal lectin-like domain followed by an epidermal growth factor-like domain and a variable number of short consensus repeat sequences similar to those found in C3/C4 binding proteins. In this report, the structure of the lyam-1 gene that encodes the LAM-1 protein was determined by isolating overlapping genomic DNA clones that hybridized with a LAM-1 cDNA probe. The lyam-1 gene spans greater than 30 kilo base pairs of DNA and is composed of at least 10 exons. The 5' end of the LAM-1 mRNA was mapped by primer extension analysis revealing a single initiation region for transcription. Exons II through X contain translated sequences; exon II encodes the translation initiation codon; exon III, the leader peptide; IV, the lectin-like domain; V, the epidermal growth factor-like domain; VI and VII, the short consensus repeat units; exon VIII, the transmembrane region; exon IX encodes seven amino acids containing a potential phosphorylation site; and exon X encodes the five remaining amino acids of the cytoplasmic tail and the long 3' untranslated region. Sequencing of LAM-1 cDNA clones derived from neutrophils revealed that the protein expressed by neutrophils would be identical in sequence with the protein expressed by lymphocytes and cDNAs that would encode different isoforms of LAM-1 protein were not detected. In addition, the level of LAM-1 expression by lymphocytes and neutrophils from two patients with paroxysmal nocturnal hemoglobinuria, a disorder in which linkage of phosphatidylinositol anchors to proteins is defective, was similar to that of normal controls. Therefore, the usage of exons II through X results in the generation of a single major LAM-1 protein product expressed by lymphocytes and neutrophils.