| First Author | Buitrago C | Year | 2011 |
| Journal | Mol Cell Endocrinol | Volume | 339 |
| Issue | 1-2 | Pages | 81-9 |
| PubMed ID | 21459125 | Mgi Jnum | J:179536 |
| Mgi Id | MGI:5302618 | Doi | 10.1016/j.mce.2011.03.022 |
| Citation | Buitrago C, et al. (2011) PKC and PTPalpha participate in Src activation by 1alpha,25OH2 vitamin D3 in C2C12 skeletal muscle cells. Mol Cell Endocrinol 339(1-2):81-9 |
| abstractText | We previously demonstrated that 1alpha,25(OH)(2)-vitamin D(3) [1alpha,25(OH)(2)D(3)] induces Src activation, which mediates the hormone-dependent ERK1/2 and p38 MAPK phosphorylation in skeletal muscle cells. In the present study, we have investigated upstream steps whereby 1alpha,25(OH)(2)D(3) may act to transmit its signal to Src. Preincubation with the PKC inhibitor Ro318220 demonstrated the participation of PKC in 1alpha,25(OH)(2)D(3)-dependent Src activation. Of interest, the hormone promoted the activation of delta the isoform of PKC. We also explored the role of PTPalpha in PKC-mediated Src stimulation. Silencing of PTPalpha with a specific siRNA suppressed Src activation induced by 1alpha,25(OH)(2)D(3). Hormone treatment increased PTPalpha (Tyr789) phosphorylation and PKC-dependent phosphatase activity. Accordingly, 1alpha,25(OH)(2)D(3) promoted serine phosphorylation of PTPalpha in a PKC-dependent manner. Confocal immunocytochemistry and co-immunoprecipitation assays revealed that the hormone induces the co-localization of Src and PTPalpha with PKC participation. Computational analysis revealed that the electrostatic interaction between Src and PTPalpha is favored when PTPalpha is phosphorylated in Tyr789. These data suggest that 1alpha,25(OH)(2)D(3) acts in skeletal muscle upstream on MAPK cascades sequentially activating PKC, PTPalpha and Src. |
