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1 John D. Dingell Veterans Affairs Medical Center and Departments of 2 Medicine and 3 Biochemistry and 4 Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201; and 5 Institute of Molecular Medicine and Genetics, Medical College of Georgia, and 6 Augusta Veterans Affairs Medical Center, Augusta, Georgia 30912
In Fischer 344 rats, induction of gastric mucosal proliferative activity, whether the
result of aging or injury or occurring after administration of
epidermal growth factor, gastrin, or bombesin, is associated with a
rise in tyrosine kinase activity and tyrosine phosphorylation of
several mucosal proteins, including a protein with a molecular mass of
53-55 kDa. We hypothesized that this phosphotyrosine membrane
protein (referred to as pp55) may play a role in regulating gastric
mucosal cell proliferation and differentiation. Purification and
subsequent immunoprecipitation studies now show that pp55 is a tyrosine
kinase. In addition, the enzyme activity in the gastric mucosa is found
to be fourfold higher in aged rats than in young rats. Incubation of
gastric mucosal membranes with transforming growth factor-
(2 × 10
8 M) stimulates
tyrosine kinase activity of pp55. Immuolocalization studies reveal that
pp55 immunoreactivity is predominantly present in mucous cells that are
located just above the proliferative zone and spasmolytic
peptide-immunoreactive mucous neck cells. Tyrosine kinase activity as
well as expression of pp55 are also greatly increased in the gastric
mucosa after hypertonic saline-induced injury, a condition that results
in stimulation of surface mucosal cell proliferation and
differentiation. Our current data suggest that pp55 is a tyrosine
kinase, likely localized to pre-surface cells. The presence of pp55 in
pre-surface mucous cells and the expression and tyrosine kinase
activity of this protein, which can be stimulated during mucosal cell
proliferation and differentiation, strongly suggest a role for pp55 in
differentiation of gastric surface mucous cells.
gastric mucosa; cell proliferation; gastric injury; spasmolytic peptide
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