| First Author | Wang Y | Year | 2015 |
| Journal | J Neurochem | Volume | 133 |
| Issue | 6 | Pages | 828-43 |
| PubMed ID | 25727698 | Mgi Jnum | J:222591 |
| Mgi Id | MGI:5644906 | Doi | 10.1111/jnc.13083 |
| Citation | Wang Y, et al. (2015) The intracellular domain of L1CAM binds to casein kinase 2alpha and is neuroprotective via inhibition of the tumor suppressors PTEN and p53. J Neurochem 133(6):828-43 |
| abstractText | Cell adhesion molecule L1 promotes neuritogenesis and neuronal survival through triggering MAPK pathways. Based on the findings that L1 is associated with casein kinase 2 (CK2), and that deficiency in PTEN promotes neuritogenesis in vitro and regeneration after trauma, we examined the functional relationship between L1 and PTEN. In parallel, we investigated the tumor suppressor p53, which also regulates neuritogenesis. Here, we report that the intracellular domain of L1 binds to the subunit CK2alpha, and that knockdown of L1 leads to CK2 dephosphorylation and an increase in PTEN and p53 levels. Overexpression of L1, but not the L1 mutants L1 (S1181N, E1184V), which reduced binding between L1 and CK2, reduced expression levels of PTEN and p53 proteins, and enhanced levels of phosphorylated CK2alpha and mammalian target of rapamycin, which is a downstream effector of PTEN and p53. Treatment of neurons with a CK2 inhibitor or transfection with CK2alpha siRNA increased levels of PTEN and p53, and inhibited neuritogenesis. The combined observations indicate that L1 downregulates expression of PTEN and p53 via direct binding to CK2alpha. We suggest that L1 stimulates neuritogenesis by activating CK2alpha leading to decreased levels of PTEN and p53 via a novel, L1-triggered and CK2alpha-mediated signal transduction pathway. L1CAM (L1 cell adhesion molecule) is implicated in neural functions through the cognate src/MAP kinase signaling pathway. We now describe a novel signaling platform operating via the alpha subunit of casein kinase 2 which binds to the intracellular domain of L1. Knockdown of L1CAM leads to increased levels of tumor suppressor PTEN (phosphatase and tensin homolog) and p53, known to inhibit neuritogenesis in vitro and recovery from trauma in vivo. By activating this enzyme, L1CAM adds to its beneficial functions by decreasing the levels of PTEN and p53. |
