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Differential signalling pathways for EGF versus PDGF activation of Erk1/2 MAP kinase and cell proliferation in brown pre-adipocytes
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
2008 (English)In: Experimental Cell Research, ISSN 0014-4827, Vol. 314, no 19, 3581-3592 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2008. Vol. 314, no 19, 3581-3592 p.
URN: urn:nbn:se:su:diva-15807DOI: 10.1016/j.yexcr.2008.09.007ISI: 000261457200014PubMedID: 18838072OAI: diva2:182327
Available from: 2008-12-10 Created: 2008-12-10 Last updated: 2010-02-11Bibliographically approved
In thesis
1. Role of caveolin-1 in brown adipose tissue
Open this publication in new window or tab >>Role of caveolin-1 in brown adipose tissue
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Caveolae are 50-100 nm invaginations in the plasma membrane. Caveolae and the protein caveolin-1 (Cav1) have been shown to be important in many signaling pathways in different cell types; however, in some cell types caveolae and Cav1 do not seem to affect the investigated signaling pathways. In my thesis, I have investigated the role of caveolin-1 (Cav1) in metabolism and b3-adrenergic, LPA-, EGF- and PDGF-receptor signaling in brown adipocytes.

Brown adipose tissue is responsible for nonshivering thermogenesis. Recent studies have shown that not only infants but also adult man can have brown adipose tissue and that the presence is negatively correlated with both obesity and age. By understanding how signaling for proliferation and differentiation in brown adipocytes is regulated, it could be possible in the future to activate brown adipose tissue to combat obesity and the metabolic syndrome.

In brown adipocytes, both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were able to induce proliferation, which was dependent on Erk1/2 activation. However, EGF and PDGF utilized different pathways to activate Erk1/2, with EGF signaling partially occurring via a Src-pathway (not involving PI3K/PKC) and PDGF via a PI3K/PKC/Src-pathway. Furthermore, LPA receptors were able to activate Erk1/2 via two pathways, one Gi/PKC/Src-pathway and one PI3K-pathway. For these receptors, Cav1-ablation did not affect the agonist-induced Erk1/2 activation. Cav1 was, however, required for proper b3-adrenergic receptor (b3-AR) signaling to cAMP and for adenylyl cyclase activity.

In Cav1-ablated mice, the adrenergic receptors are desensitized. However, this desensitization could be overcome physiologically, and the Cav1-ablated mice were therefore able to survive in prolonged cold by nonshivering thermogenesis.

In conclusion, ablation of Cav1 affected certain signaling pathways in brown adipocytes, while other pathways were not affected or could be physiologically rescued.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. 110 p.
caveolin, brown adipose tissue, metabolism, signaling
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Research subject
urn:nbn:se:su:diva-37125 (URN)978-91-7447-005-5 (ISBN)
Public defence
2010-03-12, Hörsal 107, Frescati Backe, Svante Arrhenius väg 21 A, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 3: Manuscript. Paper 4: Manuscript.Available from: 2010-02-18 Created: 2010-02-10 Last updated: 2010-02-16Bibliographically approved

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