Move adrenomedullin receptor signaling pathway & adrenomedullin receptor signaling pathway ?

[pgaudet]

Issue raised by @pgarmiri in https://github.com/geneontology/go-annotation/issues/1712

There were a few annotations of GO:0030819 ' positive regulation of cAMP biosynthetic process' to CALCRL in human (Q16602). This protein when pairing with different receptor activity modifying proteins (RAMPs) can produce calcitonin gene-related peptide (CGRP) receptors (CRLR/RAMP1) and adrenomedullin (AM) receptors (CRLR/RAMP2 or -3). In PMID: 10882736, they show that when stably coexpressed with RAMPs, CRLR-GFP appeared on the cell surface and was fully active in intracellular cAMP production and calcium mobilization. This leads to CRLR endocytosis that occurred predominantly through a clathrin-dependent pathway. (http://www.jbc.org/content/275/38/29602.full.pdf)

Now there are specific terms for these pathways (see below) that I have used replaces the offending terms, but it seems that the information that these pathways modulate cAMP production is lost.

GO:1990410 adrenomedullin receptor signaling pathway GO:1990408 calcitonin gene-related peptide receptor signaling pathway

I have compare the 2 GO terms above with GO:0007189 'adenylate cyclase-activating G-protein coupled receptor signaling pathway' (see the link below). There seem to be under different G-protein coupled receptor terms that they are not related to cAMP signaling, which is a pity.

https://www.ebi.ac.uk/QuickGO/chart?ids=GO:1990410,GO:1990408,GO:0007189

Do you think new terms /relations are needed to capture how these pathways work? Or any other suggestions or how to deal with this case?

Thanks,

Penelope

[pgaudet]

Hi @pgarmiri

Do you think adrenomedullin receptor signaling pathway & adrenomedullin receptor signaling pathway are always cAMP-mediated ? In this case I can move the terms; otherwise I can create more specific children.

Thanks, Pascale

[pgarmiri]

Hi @pgaudet , I had to look through the literature for this.. I found a couple of papers that they there is more that one mechanisms/pathways activated by the these receptors..

"CGRP intracellular signaling is a complex area, for which more work is required. While there is a common intracellular signaling pathway involving Gαs cAMP, PKA and CREB, as cited throughout this review, a range of downstream signaling factors and also other pathways (involving Gαi/a, Gαq/11, and β-arrestin signaling) have been reported (Figure 2). These have been implicated, usually in a cell-specific manner, and have been comprehensively reviewed elsewhere " (https://www.ncbi.nlm.nih.gov/pubmed/25287861)

On a different paper they authors state: "Both cAMP accumulation and Ca2+ increased responses to adrenomedullin were mediated by cholera toxin-sensitive G protein, but the two signal transduction pathways were independent....a direct action on vascular smooth muscle cells to increase intracellular cAMP and an action on endothelial cells to stimulate nitric oxide release, with both leading to vascular relaxation" (http://www.jbc.org/content/270/9/4412.full)

Thanks,

Penelope