
ヒト・パンネキシン1は、SrcキナーゼによってTyr199およびTyr309でリン酸化されない。


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Protein phosphorylation is one of the major molecular mechanisms regulating protein activity and function throughout the cell. Pannexin 1 (PANX1) is a large-pore channel permeable to ATP and other cellular metabolites. Its tyrosine phosphorylation and subsequent activation have been found to play critical roles in diverse cellular conditions, including neuronal cell death, acute inflammation, and smooth muscle contraction. Specifically, the non-receptor kinase Src has been reported to phosphorylate Tyr198 and Tyr308 of mouse PANX1 (equivalent to Tyr199 and Tyr309 of human PANX1), resulting in channel opening and ATP release. Although the Src-dependent PANX1 activation mechanism has been widely discussed in the literature, independent validation of the tyrosine phosphorylation of PANX1 has been lacking. Here, we show that commercially available antibodies against the two phosphorylation sites mentioned above—which were used to identify endogenous PANX1 phosphorylation at these two sites— are nonspecific and should not be used to interpret results related to PANX1 phosphorylation. We further provide evidence that neither tyrosine residue is a major phosphorylation site for Src kinase in heterologous expression systems. We call on the field to re-examine the existing paradigm of tyrosine phosphorylation-dependent activation of the PANX1 channel.

### Competing Interest Statement

The authors have declared no competing interest.

The LC-MS/MS data for WT human PANX1 with or without co-expressing Src-Y529F mutant is deposited in Dryad database under <https://doi.org/10.5061/dryad.4tmpg4fh7>. The raw images of the gels/immunoblots are provided as the source data for the corresponding figures.

Human Pannexin 1 Channel is NOT Phosphorylated by Src Tyrosine Kinase at Tyr199 and Tyr309

ヒト-パンネキシン1チャネルはsrcチロシンキナーゼによってtyr199およびtyr309でリン酸化されない


ヒト・パンネキシン1チャネルはSrcチロシンキナーゼによってTyr199およびTyr309でリン酸化されない
