| First Author | Ito T | Year | 1994 |
| Journal | Proc Natl Acad Sci U S A | Volume | 91 |
| Issue | 16 | Pages | 7455-9 |
| PubMed ID | 7519779 | Mgi Jnum | J:19621 |
| Mgi Id | MGI:67770 | Doi | 10.1073/pnas.91.16.7455 |
| Citation | Ito T, et al. (1994) Interleukin 3 stimulates protein synthesis by regulating double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci U S A 91(16):7455-9 |
| abstractText | In a murine interleukin 3 (IL-3)-dependent cell line, IL-3 deprivation resulted in increased autophosphorylation of double-stranded RNA-dependent protein kinase (PKR) that has been reported to inhibit protein synthesis by phosphorylating the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha). Autophosphorylation was characterized by a shift up in mobility of PKR on SDS/PAGE gels from a 60- to a 64-kDa form. In vitro kinase studies comparing the autophosphorylated 64-kDa PKR with the nonphosphorylated 60-kDa PKR confirmed that only the 64-kDa form was active for eIF-2 alpha phosphorylation. PKR activation in vivo was associated with phosphorylation of eIF-2 alpha and inhibition of protein synthesis. Addition of IL-3 to deprived cells elicited a reciprocal response characterized by the rapid dephosphorylation of PKR and eIF-2 alpha, indicating inactivation of PKR. This was rapidly followed by the full recovery of protein synthesis. Furthermore, upon IL-3 addition, a 97-kDa phosphotyrosine-containing protein becomes rapidly and transiently associated with PKR prior to dephosphorylation of PKR and eIF-2 alpha. Genistein, a tyrosine kinase inhibitor, blocks both phosphorylation of the 97-kDa phosphoprotein and protein synthesis after IL-3 addition, suggesting a role for the 97-kDa phosphoprotein in the mechanism of inactivation of PKR and stimulation of protein synthesis. Thus, IL-3 appears to positively regulate protein synthesis by inducing the inactivation of PKR in a growth factor signaling pathway. |
