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Expression of discoidin domain receptor 1 tyrosine kinase on the human bronchial epithelium

¹ First Dept of Internal Medicine and ² Dept of Cell Differentiation, IMEG, Kumamoto University School of Medicine, Kumamoto, Japan

CORRESPONDENCE: O. Sakamoto, First Dept of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, 860-0811, Japan. Fax: 81 963710582

Keywords: bronchial epithelium, discoidin domain receptor 1, receptor tyrosine kinase, type IV collagen

Received: January 12, 2000
Accepted July 14, 2000

This work was supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture of Japan.

Discoidin domain receptor 1 (DDR1) tyrosine kinases constitute a novel family of receptors characterized by a unique structure in the ectodomain (discoidin-I domain). The DDR1 ligand is the extracellular matrix protein collagen.

To identify receptor tyrosine kinases (RTKs) involved in control of growth and differentiation of human bronchial epithelial (HBE) cells, a polymerase chain reaction-based search for RTKs in HBE cells was performed. DDR1 was the most abundant clone identified. Northern analysis detected a 3.6 kb DDR1 messenger ribonucleic acid (mRNA) expressed in HBE cells and transformed HBE lines, BET-1A and BEAS-2B. In addition, fluorescence-activated cell sorter (FACS) analyses using an anti-DDR1 antibody showed that DDR1 was expressed on HBE cells and two HBE lines.

Immunohistochemical staining using human bronchial tissue demonstrated that DDR1 was mainly expressed at the basolateral cell surface of the bronchial epithelium. Furthermore, immunostaining of type IV collagen, a major component of the basement membrane, clearly showed that the basement membrane was closely attached to the basal surface of the bronchial epithelium.

Since collagen binds to and activates discoidin domain receptor 1 tyrosine kinase, colocalization of discoidin domain receptor 1 and its ligand type IV collagen demonstrates a potential interaction of discoidin domain receptor 1 on the bronchial epithelium with type IV collagen. Further study of this interaction may define the functional significance of the collagen-discoidin domain receptor 1 signalling pathway in health and in disease.