scholarly journals Localization and significance of pp55, a gastric mucosal membrane protein with tyrosine kinase activity

1998 ◽  
Vol 274 (5) ◽  
pp. G863-G870 ◽  
Author(s):  
Adhip P. N. Majumdar ◽  
James R. Goldenring
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Mucosal Cell ◽  
Mucous Cells ◽  
Tyrosine Kinase Activity ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mucosal Cell Proliferation

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-α (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.

Lidocaine Inhibits Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor and Suppresses Proliferation of Corneal Epithelial Cells

2004 ◽  
Vol 100 (5) ◽  
pp. 1206-1210 ◽  
Author(s):  
Masashi Hirata ◽  
Masahiro Sakaguchi ◽  
Chikako Mochida ◽  
Chie Sotozono ◽  
Kyoko Kageyama ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Epithelial Cell Proliferation ◽  
Tyrosine Kinase Activity ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Epidermal Growth

Background Although lidocaine is recognized as an excellent topical corneal analgesic, its toxic effect on corneal epithelial cells limits its use during corneal epithelial wound healing. Mechanism of the impairment of corneal reepithelialization with lidocaine, however, has not been evaluated. The authors' previous study revealed that lidocaine inhibits the activity of tyrosine kinase receptors through the interaction with specific amino acid sequences around autophosphorylation sites, including acidic, basic, and aromatic amino acids. Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with an important role in epithelial cell proliferation after corneal wounding, also possesses these amino acids sequences around autophosphorylation sites. The authors hypothesized that lidocaine would suppress tyrosine kinase activity of EGFR and would impair corneal epithelial cell proliferation. Methods To investigate the effect of lidocaine (4 microM-40 mM) on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR, the authors studied purified EGFR in microtubes. They cultured human corneal epithelial cells (HCECs) with EGF and lidocaine to investigate the effect of lidocaine on cell proliferation and on autophosphorylation of EGFR in HCECs. Results Lidocaine (> or =400 microM) significantly suppressed EGF-stimulated autophosphorylation of the purified EGFR. In the HCEC study, EGF alone stimulated cell proliferation and increased autophosphorylation of EGFR in HCECs. Lidocaine (> or = 400 microM) significantly suppressed both the proliferation of HCECs promoted by EGF and EGF-stimulated autophosphorylation of EGFR. Conclusion Lidocaine directly inhibits tyrosine kinase activity of EGFR and suppresses the corneal epithelial cell proliferation.

Cytosolic phospholipase A2 is activated by the hepatocyte growth factor receptor-kinase in Madin Darby canine kidney cells

1997 ◽  
Vol 110 (14) ◽  
pp. 1655-1663
Author(s):  
G.G. Skouteris ◽  
C.H. Schroder
Keyword(s):  
Arachidonic Acid ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Map Kinase ◽  
Kinase Activity ◽  
Mdck Cells ◽  
Tyrosine Kinase Activity ◽  
Cytosolic Phospholipase ◽  
Acid Release ◽  
Hepatocyte Growth

The hepatocyte growth factor/scatter factor (HGF/SF) receptor which is a transmembrane protein encoded by the Met oncogene, possesses intrinsic tyrosine kinase activity which transduces the mitogenic, morphogenic and the scattering effect of HGF/SF. The pluripotent signal of HGF/SF is transduced through association of the Met receptor with various intracellular adaptors. Phosphorylation of cytosolic phospholipase A2 (cPLA2) is associated with activation of this molecule which in turn leads to arachidonic acid production followed by release of prostaglandins and related compounds exerting their roles onto cell proliferation, chemotaxis and vascular motility. Arachidonic acid and its metabolites were shown to be involved in processes like liver regeneration where growth factor receptors possessing tyrosine kinase activity are implicated. In this study we examined whether stimulation of the HGF/SF-receptor's tyrosine kinase activity would involve changes in the phosphorylation state and the activity of cPLA2 in MDCK cells, where HGF/SF is known to induce scattering responses rather than mitogenesis. The activated p145betaMET was shown to associate with and to phosphorylate cPLA2 on tyrosine residues, this leading to subsequent release of arachidonic acid. cPLA2 was also phosphorylated in serine residues and such a role has been so far assigned to the mitogen activated protein (MAP) kinase. Our data have also shown that MAP kinase is associated and phosphorylated on tyrosine by the activated p145betaMET. Immunodepletion of MAP kinase via electroporation of an anti-MAP kinase antibody, did not significantly decrease arachidonic acid release in HGF/SF-stimulated MDCK cells. It is therefore emerging that phosphorylation of cPLA2 on tyrosine by the HGF/SF receptor kinase is capable of triggering arachidonic acid release and that MAP kinase is contributing to full, but does not drive, the activity of cPLA2. The release of arachidonic acid by MDCK cells following HGF/SF stimulation is establishing this fatty acid and its metabolites as major components involved in the transduction of MET-driven signals and at the same time in the amplification of such signals.

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