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Proc Natl Acad Sci U S A. 2008 May 20;105(20):7235-9. doi: 10.1073/pnas.0802301105. Epub 2008 May 14.

Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells.

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1
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston MA 02115, USA.

Abstract

Osteopontin (Opn) contributes to diverse biological processes that include immune responses, vascularization, and bone formation. Until recently, studies describing the activities of Opn have focused on the cytokine-like properties of the secreted protein. Here, we show that alternative translation of a single Opn mRNA species generates a secreted and intracellular isoform. Utilization of a 5' canonical translation start site generates a protein that includes an N-terminal signal sequence allowing targeting to secretory vesicles and cytokine secretion, whereas usage of a downstream start site generates a shortened protein that lacks the N-terminal signal sequence and localizes mainly to cytoplasm. The coordinated action of these Opn gene products regulates the functional phenotype of subsets of dendritic cells.

PMID:
18480255
PMCID:
PMC2438233
DOI:
10.1073/pnas.0802301105
[Indexed for MEDLINE]
Free PMC Article
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