Localization and significance of pp55, a gastric mucosal membrane protein with tyrosine kinase activity.
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-alpha (2 x 10(-8) M) stimulates tyrosine kinase activity of pp55. Immunolocalization 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.
Majumdar
A P
AP
John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan, USA.
Goldenring
J R
JR
D000375:Aging / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013450:Sulfones / Q000302:isolation & purification / Q000378:metabolism*; D014018:Tissue Distribution; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology
D008565:Membrane Proteins; D012462:Saline Solution, Hypertonic; D013450:Sulfones; D016211:Transforming Growth Factor alpha; C081650:5'-O-(((2-decanoylamino-3-phenylpropyloxycarbonyl)amino)sulfonyl)uridine; D011505:Protein-Tyrosine Kinases; D014529:Uridine