Abstract: PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biological functions. Recently, the proteic product of a nonallelic variant gene of CXCL4 was isolated from human platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in the mature protein, but exhibits a 38% amino acid divergence in the signal peptide region. We hypothesized that this may imply a difference in the cell type in which CXCL4L1 is expressed or a difference in its mode of secretion. In different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct subcellular localization and a differential regulation of secretion, CXCL4 being stored in secretory granules and released in response to protein kinase C activation, whereas CXCL4L1 was continuously synthesized and secreted through a constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes. (Blood. 2007;109:4127-4134)

PF-4/CXCL4 and CXCLAL1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion / L. Lasagni; R. Grepin; B. Mazzinghi; E. Lazzeri; C. Meini; C. Sagrinati; F. Liotta; F. Frosali; E. Ronconi; N. Alain-Courtois; L. Ballerini; G. S. Netti; E. Maggi; F. Annunziato; M. Serio; S. Romagnani; A. Bikfalvi; P. Romagnani. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 109:(2007), pp. 4127-4134.

PF-4/CXCL4 and CXCLAL1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion

LASAGNI, LAURA;MAZZINGHI, BENEDETTA;LAZZERI, ELENA;SAGRINATI, COSTANZA;LIOTTA, FRANCESCO;FROSALI, FRANCESCA;RONCONI, ELISA;BALLERINI, LARA;MAGGI, ENRICO;ANNUNZIATO, FRANCESCO;SERIO, MARIO;ROMAGNANI, SERGIO;ROMAGNANI, PAOLA
2007

Abstract

Abstract: PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biological functions. Recently, the proteic product of a nonallelic variant gene of CXCL4 was isolated from human platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in the mature protein, but exhibits a 38% amino acid divergence in the signal peptide region. We hypothesized that this may imply a difference in the cell type in which CXCL4L1 is expressed or a difference in its mode of secretion. In different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct subcellular localization and a differential regulation of secretion, CXCL4 being stored in secretory granules and released in response to protein kinase C activation, whereas CXCL4L1 was continuously synthesized and secreted through a constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes. (Blood. 2007;109:4127-4134)
2007
109
4127
4134
L. Lasagni; R. Grepin; B. Mazzinghi; E. Lazzeri; C. Meini; C. Sagrinati; F. Liotta; F. Frosali; E. Ronconi; N. Alain-Courtois; L. Ballerini; G. S. Netti; E. Maggi; F. Annunziato; M. Serio; S. Romagnani; A. Bikfalvi; P. Romagnani
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/335981
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