p-S373-GJA1:p-S-ITGA5:ITGB1 (p-S373-Connexin-43:p-S-Integrin alpha5:Integrin beta1) transports prostaglandin E2 (PGE2) from the cytosol to the extracellular region

Stable Identifier
R-HSA-9857682
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Mechanical strain on osteocytes causes the osteocytes to release prostaglandin E2 (PGE2) (inferred from mouse cells) and this release is at least partly due to opening of Connexin 43 (Cx43, GJA1) hemichannels, as downregulation of Gja1 expression (Cherian et al. 2005) or blockage of Gja1 hemichannels (Siller-Jackson et al. 2008) in mouse osteocytes causes a decrease in PGE2 release. The opening of the Gja1 hemichannels in the cell bodies of mouse osteocytes is due to phosphorylation of Gja1 on serine-373 by Akt1 (Batra et al. 2014), which is activated by mechanosensors in the dendrites of the osteocytes (reviewed in Zhao et al. 2023). Additional mechanisms of PGE2 release may exist, as knockout of Gja1 in mouse osteocytes did not abolish PGE2 release (Thi et al. 2012).
Estimates of the pore size of GJA1 channels raises the question of whether they are capable of transporting PGE2, therefore the effect of GJA1 on PGE2 transport may be indirect (reviewed in Zhao et al. 2023).
Participants
Participates
Catalyst Activity

channel activity of p-S373-GJA1:p-S-ITGA5:ITGB1 [plasma membrane]

Inferred From
Cross References
RHEA
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