title: Pituitary adenylate cyclase-activating polypeptide causes increased tyrosine phosphorylation of focal adhesion kinase and paxillin.
abstract: The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin were investigated using lung cancer cells. Addition of PACAP-27 or PACAP-38 but not vasoactive intestinal peptide to NCI-H838 or NCI-H1299 human lung cancer cells significantly increased the tyrosine phosphorylation of FAK or paxillin. The increase in FAK or paxillin tyrosine phosphorylation caused by addition of PACAP-27 to NCI-H838 cells was inhibited by PACAP(6-38), a PAC1-receptor (R) antagonist. The increase in FAK or paxillin tyrosine phosphorylation caused by 100 nM PACAP-27 was maximal 2 min after addition to NCI-H838 cells. The effects of PACAP at stimulating FAK and paxillin tyrosine phosphorylation were reversed by cytochalasin D and genistein which inhibit actin polymerization and tyrosine kinase activity, respectively. The effects of PACAP at stimulating FAK and paxillin tyrosine phosphorylation were reversed by U-73122 but not H89 which inhibit phospholipase C and protein kinase A, respectively. The results show that PAC1-R regulates FAK and paxillin tyrosine phosphorylation in lung cancer cells as a result of increased phosphatidylinositol turnover but not adenylyl cylase stimulation.
authors: Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. moodyt@mail.nih.gov
authors: Terry W
authors: TW
authors: Moody
authors: Julius
authors: J
authors: Leyton
authors: Robert T
authors: RT
authors: Jensen
mesh_terms: D045744:Cell Line, Tumor; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D051419:Paxillin / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C495401:ADCYAP1 protein, human; D051419:Paxillin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human