Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C.
Annexin 1 (ANXA1) is an important mediator of glucocorticoid action in the neuroendocrine system. As the activity of this protein in other systems is modulated by phosphorylation of its N-terminal domain, we have explored the significance of this domain and its phosphorylation status to ANXA1 action...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2002
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| _version_ | 1826257405922508800 |
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| author | John, C Cover, P Solito, E Morris, J Christian, H Flower, R Buckingham, J |
| author_facet | John, C Cover, P Solito, E Morris, J Christian, H Flower, R Buckingham, J |
| author_sort | John, C |
| collection | OXFORD |
| description | Annexin 1 (ANXA1) is an important mediator of glucocorticoid action in the neuroendocrine system. As the activity of this protein in other systems is modulated by phosphorylation of its N-terminal domain, we have explored the significance of this domain and its phosphorylation status to ANXA1 actions within the pituitary gland, using an established in vitro preparation. Two N-terminal peptides, ANXA1(Ac2-26) and ANXA1(Ac1-50), inhibited forskolin-evoked ACTH and prolactin release; however, they lacked the potency and full efficacy of the parent molecule (ANXA1(1-346)), whereas other shorter N-terminal sequences were without effect. A chimeric protein comprising ANXA1(1-44) and the C-terminal core of ANXA5 (ANXA5(20-320)) also produced a partial inhibition of peptide release. Protein kinase C (PKC) blockade (PKC(19-36)) abolished the inhibitory effects of dexamethasone on forskolin-evoked peptide release and attenuated the antisecretory actions of ANXA1(Ac2-26.) ANXA5, which sequesters PKC in other systems, produced similar effects. PKC(19-36) also blocked the dexamethasone- induced translocation of a serine phosphorylated species of ANXA1 from the cytoplasm to the outer cell surface. These results suggest that 1) the N-terminal domain plays a fundamental role in effecting the inhibitory actions of ANXA1 on pituitary peptide release; 2) PKC-dependent mechanisms are essential for both the cellular exportation and the biological activity of ANXA1; and 3) ANXA1 exported from the cells is serine phosphorylated. |
| first_indexed | 2024-03-06T18:17:42Z |
| format | Journal article |
| id | oxford-uuid:05300d76-14c1-452f-bb4f-ae84ae88b112 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:17:42Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:05300d76-14c1-452f-bb4f-ae84ae88b1122022-03-26T08:55:47ZAnnexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:05300d76-14c1-452f-bb4f-ae84ae88b112EnglishSymplectic Elements at Oxford2002John, CCover, PSolito, EMorris, JChristian, HFlower, RBuckingham, JAnnexin 1 (ANXA1) is an important mediator of glucocorticoid action in the neuroendocrine system. As the activity of this protein in other systems is modulated by phosphorylation of its N-terminal domain, we have explored the significance of this domain and its phosphorylation status to ANXA1 actions within the pituitary gland, using an established in vitro preparation. Two N-terminal peptides, ANXA1(Ac2-26) and ANXA1(Ac1-50), inhibited forskolin-evoked ACTH and prolactin release; however, they lacked the potency and full efficacy of the parent molecule (ANXA1(1-346)), whereas other shorter N-terminal sequences were without effect. A chimeric protein comprising ANXA1(1-44) and the C-terminal core of ANXA5 (ANXA5(20-320)) also produced a partial inhibition of peptide release. Protein kinase C (PKC) blockade (PKC(19-36)) abolished the inhibitory effects of dexamethasone on forskolin-evoked peptide release and attenuated the antisecretory actions of ANXA1(Ac2-26.) ANXA5, which sequesters PKC in other systems, produced similar effects. PKC(19-36) also blocked the dexamethasone- induced translocation of a serine phosphorylated species of ANXA1 from the cytoplasm to the outer cell surface. These results suggest that 1) the N-terminal domain plays a fundamental role in effecting the inhibitory actions of ANXA1 on pituitary peptide release; 2) PKC-dependent mechanisms are essential for both the cellular exportation and the biological activity of ANXA1; and 3) ANXA1 exported from the cells is serine phosphorylated. |
| spellingShingle | John, C Cover, P Solito, E Morris, J Christian, H Flower, R Buckingham, J Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C. |
| title | Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C. |
| title_full | Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C. |
| title_fullStr | Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C. |
| title_full_unstemmed | Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C. |
| title_short | Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C. |
| title_sort | annexin 1 dependent actions of glucocorticoids in the anterior pituitary gland roles of the n terminal domain and protein kinase c |
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