The G Protein-Coupled Receptor PAC1 Regulates Transactivation of the Receptor Tyrosine Kinase HER3.
Carcinoma, Non-Small-Cell Lung
/ metabolism
Cell Line, Tumor
Cell Proliferation
ErbB Receptors
/ antagonists & inhibitors
Humans
Lung Neoplasms
/ metabolism
Phosphorylation
Pituitary Adenylate Cyclase-Activating Polypeptide
/ metabolism
Receptor, ErbB-2
/ antagonists & inhibitors
Receptor, ErbB-3
/ antagonists & inhibitors
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
/ metabolism
HER3
Lung cancer
PAC1
Proliferation
Transactivation
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
26
06
2020
accepted:
14
09
2020
pubmed:
24
9
2020
medline:
6
1
2022
entrez:
23
9
2020
Statut:
ppublish
Résumé
Peptide G protein-coupled receptors (GPCRs) for pituitary adenylate cyclase activating polypeptide (PACAP) regulate the growth of non-small cell lung cancer (NSCLC) cells. PACAP binds with high affinity to PAC1, which causes transactivation of receptor tyrosine kinases (RTK) for the EGFR and HER2 but its effect on HER3 is unknown. Using 3 NSCLC cell lines (NCI-H358, NCI-H441, and Calu-3), proteins for EGFR, HER2, HER3, and PAC1 were detected. The increase in EGFR tyrosine phosphorylation caused by PACAP was blocked by the EGFR tyrosine kinase inhibitor (TKI) gefitinib, or PACAP(6-38), a PAC1 antagonist. The increase in HER2 tyrosine phosphorylation caused by PACAP was inhibited by trastuzumab, a monoclonal antibody (mAb) for HER2, or PACAP(6-38). The increase in HER3 tyrosine phosphorylation caused by PACAP was inhibited by HER3 mAb3481 or PACAP(6-38). Immunoprecipitation experiments indicated the PACAP addition to Calu-3 cells resulted in the formation of EGFR/HER3 and HER2/HER3 heterodimers. Addition of the HER3 agonist neuregulin (NRG)-1 increased HER3 tyrosine phosphorylation in non-small-cell lung cancer (NSCLC) cells. PACAP or NRG-1 increased the proliferation of NSCLC cells, whereas PACAP(6-38), gefitinib, trastuzumab, or mAb3481 inhibited proliferation. The results indicate that PAC1 regulates the proliferation of NSCLC cells as a result of transactivation of the EGFR, HER2, and HER3.
Identifiants
pubmed: 32964398
doi: 10.1007/s12031-020-01711-8
pii: 10.1007/s12031-020-01711-8
pmc: PMC8844836
mid: NIHMS1777403
doi:
Substances chimiques
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
0
EGFR protein, human
EC 2.7.10.1
ERBB2 protein, human
EC 2.7.10.1
ERBB3 protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Receptor, ErbB-3
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1589-1597Subventions
Organisme : Intramural NIH HHS
ID : Z99 DK999999
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DK053100
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DK053101
Pays : United States
Informations de copyright
© 2020. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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