| First Author | Wang Q | Year | 2016 |
| Journal | Biochem J | Volume | 473 |
| Issue | 4 | Pages | 397-410 |
| PubMed ID | 26611753 | Mgi Jnum | J:237666 |
| Mgi Id | MGI:5816429 | Doi | 10.1042/BJ20150907 |
| Citation | Wang Q, et al. (2016) A ternary complex comprising FAK, PTPalpha and IP3 receptor 1 functionally engages focal adhesions and the endoplasmic reticulum to mediate IL-1-induced Ca2+ signalling in fibroblasts. Biochem J 473(4):397-410 |
| abstractText | Ca(2+) release is tightly sequestered in eukaryotic cells to enable fine spatio-temporal control of signalling but how Ca(2+) release from the endoplasmic reticulum (ER) is linked to cell adhesions is not defined. We examined the spatial restriction of Ca(2+) release through the inositol 1,4,5-triphosphate receptor 1 (IP3R1) in response to interleukin-1 (IL-1) and the functions of the adhesion-associated proteins, focal adhesion kinase (FAK) and protein tyrosine phosphatase-alpha (PTPalpha). In cultured fibroblasts IL-1 treatment promoted co-localization of PTPalpha and FAK with the ER and increased association of IP3R1 with PTPalpha and FAK at focal adhesions (FAs). GST pull-down assays of purified proteins demonstrated that PTPalpha and FAK directly interacted with IP3R1. These interactions depended on the focal adhesion-targeting (FAT) and band4.1-ezrin-radixin-moesin (FERM) domains of FAK. PTPalpha was required for the association of IP3R1 with Src, which mediated IP3R1 phosphorylation and consequently ER Ca(2+) release. Collectively, these data indicate that PTPalpha and FAK, which are enriched in FAs, interact with IP3R1 at adjacent ER sites to spatially sequester IL-1-induced Ca(2+) signalling. |
