| First Author | Zwaenepoel O | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 2 | Pages | 691-706 |
| PubMed ID | 22084313 | Mgi Jnum | J:180607 |
| Mgi Id | MGI:5306699 | Doi | 10.1096/fj.11-189753 |
| Citation | Zwaenepoel O, et al. (2012) Functional CSF-1 receptors are located at the nuclear envelope and activated via the p110delta isoform of PI 3-kinase. FASEB J 26(2):691-706 |
| abstractText | Colony stimulating factor-1 (CSF-1) and its receptor (CSF-1R) are key regulators of macrophage biology, and their elevated expression in cancer cells has been linked to poor prognosis. CSF-1Rs are thought to function at the plasma membrane. We show here that functional CSF-1Rs are present at the nuclear envelope of various cell types, including primary macrophages, human cancer cell lines, and primary human carcinomas. In response to CSF-1, added to intact cells or isolated nuclei, nucleus-associated CSF-1R became phosphorylated and triggered the phosphorylation of Akt and p27 inside the nucleus. Extracellularly added CSF-1 was also found to colocalize with nucleus-associated CSF-1Rs. All these activities were found to depend selectively on the activity of the p110delta isoform of phosphoinositide 3-kinase (PI3K). This finding was related to the p110delta-dependent translocation of exogenous CSF-1 to the nucleus-associated CSF-1Rs, correlating with a prominent role of p110delta in activation of the Rab5 GTPase, a key regulator of the endocytic trafficking. siRNA-silencing of Rab5a phenocopied p110delta inactivation and nuclear CSF-1 signaling. Our work demonstrates for the first time the presence of functional nucleus-associated CSF-1Rs, which are activated by extracellular CSF-1 by a mechanism that involves p110delta and Rab5 activity. These findings may have important implications in cancer development.-Zwaenepoel, O., Tzenaki, N., Vergetaki A., Makrigiannakis, A., Vanhaesebroeck, B., Papakonstanti, E. A. Functional CSF-1 receptors are located at the nuclear envelope and activated via the p110delta isoform of PI 3-kinase. |
