Focal adhesion kinase, paxillin, and bcl-2: analysis of expression, phosphorylation, and association during morphogenesis.
Cell adhesive mechanisms which determine tissue architecture during morphogenesis are tightly regulated and have an impact on apoptosis, cell migration, proliferation, and differentiation. Bcl-2 is a death repressor that protects cells from apoptosis initiated by a variety of stimuli including loss of cell adhesion. Utilizing the kidney as a model of an organ that undergoes three-dimensional development we demonstrate that bcl-2 directly associates with paxillin. Focal adhesion kinase (FAK)(p125) and paxillin(p68) were highly expressed and tyrosine phosphorylated during development but declined to low levels following renal maturation (postnatal day 20) in normal mice. The decline in the expression of p125 FAK and p68 paxillin occurred together with an increase in specific cleavage products of lower molecular weights. Mice deficient in bcl-2 are born with renal hypoplasia and succumb to renal failure as a result of renal multicystic disease. In kidneys from postnatal day 20 bcl-2 -/- mice, tyrosine phosphorylation of p125 FAK and p68 paxillin was not down-regulated. However, the level of expression was similar to that of normal mice. These results demonstrate that the developmentally regulated expression and phosphorylation of FAK and paxillin, in the presence of bcl-2, is necessary for normal morphogenesis. The interaction of paxillin with bcl-2 during nephrogenesis may provide an alternative to integrin(s) signaling through paxillin/FAK thus bypassing the need for adhesion-mediated survival during three dimensional morphogenesis. Dev Dyn 1999;215:371-382.
George M. O'Brien Kidney and Urological Diseases Center, Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. sorenson@biochem.wustl.edu
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D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018507:Gene Expression Regulation, Developmental; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology; D007680:Kidney Neoplasms / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009024:Morphogenesis; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013997:Time Factors; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015815:Cell Adhesion Molecules; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D007074:Immunoglobulin G; D051419:Paxillin; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; C496062:Pxn protein, mouse; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse