{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:25Z","timestamp":1787017765431,"version":"build-2736575974"},"reference-count":62,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>\n                    Integrin-associated focal adhesion complex formation and turnover plays an essential role in directing interactions between epithelial cells and the extracellular matrix during organogenesis, leading to appropriate cell spreading, cell-matrix adhesion, and migration. Autosomal recessive polycystic kidney disease (ARPKD) is associated with loss of function of PKHD1-encoded protein fibrocystin-1 and is characterized by cystic dilation of renal collecting tubules (CT) in utero and loss of renal function in patients if they survive the perinatal period. Normal polycystin-1 (PC-1)\/focal adhesion complex function is required for control of CT diameter during renal development, and abnormalities in these complexes have been demonstrated in human PC-1 mutant cystic cells. To determine whether loss of fibrocystin-1 was associated with focal adhesion abnormalities, ARPKD cells or normal age-matched human fetal (HF)CT cells in which fibrocystin-1 had been decreased by 85% by small interfering RNA inhibition were compared with normal HFCT. Accelerated attachment and spreading on collagen matrix and decreased motility of fibrocystin-1-deficient cells were associated with longer paxillin-containing focal adhesions, more complex actin-cytoskeletal rearrangements, and increased levels of total \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -integrin, c-Src, and paxillin. Immunoblot analysis of adhesive cells using site-specific phospho-antibodies demonstrated ARPKD-associated loss of activation of focal adhesion kinase (FAK) by phosphorylation at its autophosphorylation site (Y397); accelerated FAK inhibition by phosphorylation at Y407, S843, and S910; as well as increased activation of c-Src at pY418. Paxillin coimmunoprecipitation analyses suggested that fibrocystin-1 was a component of the normal focal adhesion complex and that actin and fibrocystin-1 were lost from ARPKD complexes.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00032.2009","type":"journal-article","created":{"date-parts":[[2009,11,18]],"date-time":"2009-11-18T22:19:04Z","timestamp":1258582744000},"page":"C831-C846","source":"Crossref","is-referenced-by-count":37,"title":["Abnormalities in focal adhesion complex formation, regulation, and function in human autosomal recessive polycystic kidney disease epithelial cells"],"prefix":"10.1152","volume":"298","author":[{"given":"Sharon","family":"Israeli","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Amsler","sequence":"additional","affiliation":[{"name":"Department of Medicine, 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