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J. Biol. Chem., Vol. 265, Issue 14, 7760-7767, 05, 1990
DC Ord, TJ Ernst, LJ Zhou, A Rambaldi, O Spertini, J Griffin and TF Tedder
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.
Structure of the gene encoding the human leukocyte adhesion molecule-1 (TQ1, Leu-8) of lymphocytes and neutrophils
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
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