Growth factors stimulate kidney proximal tubule cell migration independent of augmented tyrosine phosphorylation of focal adhesion kinase

• Published in: Biochemical and biophysical research communications 2005-03, Vol.328 (2), p.560-566
• Main Authors: Cao, Yangming, Baig, Masood R., Hamm, L. Lee, Wu, Kuoting, Simon, Eric E.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Cell Line; Cell migration; Cell Movement - drug effects; Cell Movement - physiology; Epidermal growth factor; Epidermal Growth Factor - pharmacology; Focal adhesion kinase; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Growth Substances - pharmacology; Hepatocyte growth factor; Hepatocyte Growth Factor - pharmacology; Humans; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factor-1; Kidney proximal tubule cells; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - physiology; Mice; Phosphorylation - drug effects; Phosphotyrosine; Protein-Tyrosine Kinases - metabolism; Tyrosine - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.01.010

Migration of human proximal tubule cells (HKC-5) was stimulated by epidermal growth factor (EGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1). Integrin signaling via phosphorylation of focal adhesion kinase (FAK) appears to play a central role in cell migration. Once stimulated, FAK undergoes autophosphorylation at tyrosine (Y) 397, followed by phosphorylation of several sites including Y576/Y577 which increases FAK’s kinase activity, as well as at Y407, Y861, and Y925. EGF, HGF, and IGF-1 stimulate FAK phosphorylation in various cells. We showed that endothelin stimulated phosphorylation of Y397 in fibroblasts but not HKC-5 cells. After EGF stimulation, HKC-5 cells showed no change in tyrosine phosphorylation at FAK Y397, 407, 576, 861, or 925. Similarly, HGF and IGF-1 did not stimulate the phosphorylation of FAK Y397 in HKC-5 cells. Further, after inhibition of FAK expression by siRNA, cell migration was similar to cells treated with non-target siRNA and responded to EGF with increased migration. Thus, in proximal tubule cells, stimulation of cell migration by growth factors was independent of augmented FAK tyrosine phosphorylation.