Activation of surfactant protein-B transcription: Signaling through the SP-A receptor utilizing the PI3 kinase pathway (original) (raw)

Journal of Cellular Physiology, 2000

Abstract

This study describes receptor-activated signaling initiated by surfactant protein-A (SP-A), and the means by which it activates transcription of surfactant protein-B. Pulmonary surfactant is a mixture of lipids and associated proteins produced by type II pneumocytes. Interaction of SP-A with its cognate receptor (SPAR) on type II cells is involved in regulating surfactant secretion. This interaction also increases transcription of surfactant proteins and several other genes. To study SP-A cytokine activity, we used as a model surfactant-protein (SP-B) transcription, the activators of which have been characterized. HNF-3 and TTF-1 transcription factors are known to stimulate SP-B transcription. SP-A caused increased phosphorylation and nuclear localization of both. Corresponding increases in protein binding to the SP-B promoter were demonstrated by gel shift analysis. SP-A increased protein binding to HNF-3 and TTF-1 consensus recognition elements. Footprinting analysis indicated that SP-A-induced protein binding to SP-B promoter was greater in amount, but not different in location, from that seen in control cells, which normally transcribe SP-B. SP-A caused transient increases in PI3 kinase localization at the plasma membrane, and SP-A signaling to elicit increased SP-B transcription was blocked by LY294002, an inhibitor of PI3 kinase. Therefore, SP-A signals through PI3 kinase to increase SP-B transcription in type II pneumocytes by enhancing TTF-1 and HNF-3 activation of the SP-B promoter. SP-A activation of this signaling pathway, which affects many cellular functions and has not previously been implicated in type II cell transcriptional activity, has profound import for understanding type II cell biology.

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