| First Author | Buitrago L | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 40 | Pages | 29160-9 |
| PubMed ID | 23960082 | Mgi Jnum | J:205968 |
| Mgi Id | MGI:5547480 | Doi | 10.1074/jbc.M113.464107 |
| Citation | Buitrago L, et al. (2013) Tyrosine phosphorylation on spleen tyrosine kinase (Syk) is differentially regulated in human and murine platelets by protein kinase C isoforms. J Biol Chem 288(40):29160-9 |
| abstractText | Protein kinase C (PKC) isoforms differentially regulate platelet functional responses downstream of glycoprotein VI (GPVI) signaling, but the role of PKCs regulating upstream effectors such as Syk is not known. We investigated the role of PKC on Syk tyrosine phosphorylation using the pan-PKC inhibitor GF109203X (GFX). GPVI-mediated phosphorylation on Syk Tyr-323, Tyr-352, and Tyr-525/526 was rapidly dephosphorylated, but GFX treatment inhibited this dephosphorylation on Tyr-525/526 in human platelets but not in wild type murine platelets. GFX treatment did not affect tyrosine phosphorylation on FcRgamma chain or Src family kinases. Phosphorylation of Lat Tyr-191 and PLCgamma2 Tyr-759 was also increased upon treatment with GFX. We evaluated whether secreted ADP is required for such dephosphorylation. Exogenous addition of ADP to GFX-treated platelets did not affect tyrosine phosphorylation on Syk. FcgammaRIIA- or CLEC-2-mediated Syk tyrosine phosphorylation was also potentiated with GFX in human platelets. Because potentiation of Syk phosphorylation is not observed in murine platelets, PKC-deficient mice cannot be used to identify the PKC isoform regulating Syk phosphorylation. We therefore used selective inhibitors of PKC isoforms. Only PKCbeta inhibition resulted in Syk hyperphosphorylation similar to that in platelets treated with GFX. This result indicates that PKCbeta is the isoform responsible for Syk negative regulation in human platelets. In conclusion, we have elucidated a novel pathway of Syk regulation by PKCbeta in human platelets. |
