Nerve growth factor (NGF) induces a rapid and sustained downregulation of the focal adhesion kinase (FAK).
1. Exposure of PC12 cells to nerve growth factor (NGF) induces an early tyrosine phosphorylation of many proteins, a number of which is still unidentified. Although NGF is known to bind to and activate the receptor tyrosine kinase TrkA, many downstream targets of NGF signaling may be possibly phosphorylated by nonreceptor tyrosine kinases such as c-Src and focal adhesion kinase (FAK). 2. In the present study, exposure of TrkA-overexpressing PC12 cells to NGF is found to cause a rapid and sustained loss in the recovery of a subpopulation of nominally active FAK (i.e., being autophosphorylated on the positive site of regulation). 3. Consistent with the possibility that NGF induces the proteolysis of FAK via recruitment of Src family kinases, the use of various phosphorylation site-specific anti-FAK antibodies revealed an NGF-inducible and PP1-sensitive accumulation of a putative fragment (i.e., p62) of FAK. Significantly, the mitogenic epidermal growth factor (EGF) failed to induce the downregulation of FAK and the accumulation of tyrosine phosphorylated p62. Such differential response of FAK to NGF and EGF may shape the specificity by which these growth factors control the status of cell-matrix adhesion and the adhesion-driven signaling.
Gatti
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Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA. andreagatti4@libero.it
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism
D000906:Antibodies; D010446:Peptide Fragments; D014443:Tyrosine; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D019061:src-Family Kinases