PROK1 induction of RCAN1-4 and IL-8

Schematic representation of PROK1 induction of RCAN1-4 and IL-8. Activation of the PROKR1 by PROK1 results in the induction of IL-8 and RCAN1-4 expression. This occurs via coupling of PROKR1 to Gq protein. Activation of PLCβ by Gqα results in the production of IP3 which can then bind to IP3R in the ER and result in an efflux of calcium from the ER into the cytoplasm. In addition, the opening of calcium channels in the cell surface can also contribute to the increase in Ca2+i. This increase in Ca2+i results in calmodulin saturation, which in turn activates calcineurin. Activated calcineurin then dephosphorylates cytoplasmic NFAT. Dephosphorylated NFAT can then migrate to the nucleus and bind to binding motifs in the promoter region of RCAN1-4 and IL-8 and induce their transcription. NFAT-induced transcription of IL-8 occurs in conjunction with AP-1. The accumulation of RCAN1-4 protein results in its binding to calcineurin and the inhibition of NFAT dephosphorylation by calcineurin which prevents further expression of IL-8 and RCAN1-4. Gqα = Gq protein alpha subunit, βγ = G protein beta gamma subunits, PLCβ = phopholipase C beta, IP3 = inositol-1,4,5-triphosphate, IP3R = IP3 receptor, ER = endoplasmic reticulum, Ca2+i = intracellular ionized calcium, Cam = calmodulin, CnB = calcineurin regulatory subunit, CnA = calcineurin catalytic subunit, NFAT = nuclear factor of activated T-cells, AP-1 = activator protein 1.

Publication

Prokineticin 1 modulates IL-8 expression via the calcineurin/NFAT signaling pathway. (2009) David Maldonado-Pérez, et al. Biochim Biophys Acta. 2009 Jul;1793(7):1315-1324. Figure: F6. All organisms Homo sapiens Oryctolagus cuniculus Bos taurus Capra hircus Mus musculus Drosophila melanogaster Arabidopsis thaliana

Disease mentions