Identification and characterisation of a novel integrin beta subunit: Beta 7

Abstract

The identification of a novel human integrin $/beta$ subunit, $/beta/sb7$, has been reported in this dissertation. The full-length human $/beta/sb7$ cDNA contains 2798 nucleotides encoding a single long open reading frame of 798 amino acid residues of which 708 are extracellular and 52 are cytoplasmic. The human $/beta/sb7$ sequence displays strong homology with other integrin $/beta$ subunits, being most related to $/beta/sb2$. Cell distribution studies suggest that the expression of transcripts encoding the human $/beta/sb7$ subunit is restricted to leukocytes. This study was the first to show that the cysteine-rich repeats of the human integrin $/beta/sb7$ subunit and other integrin $/beta$ subunits are related to domain III of the laminin B chains. Furthermore, the integrin $/beta$ subunit and laminin cysteine-rich repeats are each related to the epidermal growth factor (EGF)-like repeats found in a growing number of adhesion molecules and regulatory proteins. The mouse homologue of the human $/beta/sb7$ subunit has also been cloned in this study, and it shares 87% amino acid identity with the human $/beta/sb7$ sequence. The mouse $/beta/sb7$ mRNA transcripts, like that of the human $/beta/sb7$, have a predominantly leukocyte-restricted expression, but in some haematopoietic lineage cell lines, in addition to the predominant 3 kb transcript, a less abundant 2 kb transcript is also detectable. Cultured mouse skin epithelial cells contain only the 2 kb transcript. The genes encoding the human and mouse $/beta/sb7$ subunits were mapped to human chromosome 12 (ITGB7) and mouse chromosome 15 (Itgb-7). The Itgb-7 gene was localised to the distal part of mouse chromosome 15, and exists in the gene order: Myc-Wnt-1-Itgb-1. The N-terminal 13 amino acids of the mature mouse $/beta/sb7$ subunit was shown to be identical to a 13 amino acid N-terminal sequence reported for the Mr 120,000 $/beta$ subunit of the M290 antigen, which is found highly expressed on mouse intestinal intraepithelial lymphocytes (IEL). This finding suggests that the integrin $/beta/sb7$ subunit may play important roles in IEL migration, and immunosurveillance in the gut mucosa.