Abstract |
The signal transduction mechanisms of pituitary adenylate cyclase activating polypeptide ( PACAP) were investigated in lung cancer cells. Previously, PACAP-27 addition to NCI-H838 cells increased phosphatidylinositol turnover and intracellular cAMP leading to proliferation of lung cancer cells. Also, PACAP receptors (PAC1) regulated the tyrosine phosphorylation of ERK, focal adhesion kinase, and paxillin. In this communication, the effects of PACAP on cytosolic Ca(2+) and PYK-2 tyrosine phosphorylation were investigated. PACAP-27 increased cytosolic Ca(2+) within seconds after addition to FURA-2 AM loaded NCI-H838 cells. The increase in cytosolic Ca(2+) caused by PACAP was inhibited by PACAP(6-38) (PAC1 antagonist), U73122 ( phospholipase C inhibitor), or BAPTA ( calcium chelator), but not H89 ( PKA inhibitor). PACAP-38, but not vasoactive intestinal peptide (VIP), addition to NCI-H838 or H1299 cells significantly increased the tyrosine phosphorylation of PYK-2 after 2 min. The increase in PYK-2 tyrosine phosphorylation caused by PACAP was inhibited by PACAP(6-38), U73122, or BAPTA, but not H89. The results suggest that PAC1 regulates PYK-2 tyrosine phosphorylation in a calcium-dependent manner.
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Authors | Terry W Moody, Alessia Di Florio, Robert T Jensen |
Journal | Journal of molecular neuroscience : MN
(J Mol Neurosci)
Vol. 48
Issue 3
Pg. 660-6
(Nov 2012)
ISSN: 1559-1166 [Electronic] United States |
PMID | 22581436
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Chemical References |
- ADCYAP1 protein, human
- Chelating Agents
- Estrenes
- Isoquinolines
- Neoplasm Proteins
- Peptide Fragments
- Phosphodiesterase Inhibitors
- Pituitary Adenylate Cyclase-Activating Polypeptide
- Protein Kinase Inhibitors
- Pyrrolidinones
- Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
- Sulfonamides
- 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
- Phosphotyrosine
- Egtazic Acid
- Focal Adhesion Kinase 2
- 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
- N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
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Topics |
- Calcium Signaling
(drug effects, physiology)
- Cell Line, Tumor
(drug effects, metabolism)
- Chelating Agents
(pharmacology)
- Cytosol
(drug effects, metabolism)
- Egtazic Acid
(analogs & derivatives, pharmacology)
- Estrenes
(pharmacology)
- Focal Adhesion Kinase 2
(metabolism)
- Humans
- Isoquinolines
(pharmacology)
- Lung Neoplasms
(pathology)
- Neoplasm Proteins
(metabolism)
- Peptide Fragments
(pharmacology)
- Phosphodiesterase Inhibitors
(pharmacology)
- Phosphorylation
(drug effects)
- Phosphotyrosine
(metabolism)
- Pituitary Adenylate Cyclase-Activating Polypeptide
(antagonists & inhibitors, pharmacology)
- Protein Kinase Inhibitors
(pharmacology)
- Protein Processing, Post-Translational
(drug effects)
- Pyrrolidinones
(pharmacology)
- Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
(drug effects, physiology)
- Sulfonamides
(pharmacology)
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