proadrenomectullin N-terminal 20 peptide iilrcnomi'di llir.

-CONH, adrenomedullin

Fig. 5. Schematic diagram of the AM gene and precursor and the structures and biosynthesis of AM and proadrenomedullin N-terminal 20 peptide (PAMP).

That AP-2 mediates transcriptional activation induced by protein kinase C and cAMP suggests that expression of the AM gene is modulated by signal-transduction pathways in which they are components (Imagawa et al., 1987). Given that AM stimulates production cAMP in platelets, the multiple AP-2 sites further suggests the existence of a feedback mechanism affecting AM gene expression. Within intron 1, moreover, there is a consensus sequence for the cAMP-regulated enhancer (CRE) (Fink et al., 1988), which may also be involved in the putative feedback regulation of AM gene expression by cAMP, and nuclear factor-kB (NF-kB) sites have been identified within the AM promoter. In addition, a study of the functional elements of the AM gene revealed that nuclear factor for interleukin-6 (NF-IL-6), AP-2 and the TATA box are all important in the transcriptional regulation of the AM gene (Ishimitsu et al., 1998). Thus, the human AM gene contains components for the regulation of its functional expression, which may be modulated by the activity of protein kinase C and feedback by cAMP.

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