| First Author | Misra UK | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 39 | Pages | 36509-20 |
| PubMed ID | 12114513 | Mgi Jnum | J:79286 |
| Mgi Id | MGI:2387735 | Doi | 10.1074/jbc.M203543200 |
| Citation | Misra UK, et al. (2002) The Role of cAMP-dependent Signaling in Receptor-recognized Forms of alpha 2-Macroglobulin-induced Cellular Proliferation. J Biol Chem 277(39):36509-20 |
| abstractText | Ligation of alpha(2)-macroglobulin receptors by receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) activates various signaling cascades and promotes cell proliferation. It also elevates cAMP in murine peritoneal macrophages. We now report that a significant elevation of cAMP-response element-binding protein (CREB) occurs in alpha(2)M*-stimulated cells, and this effect is potentiated by isobutylmethylxanthine, dibutyryl-cAMP, or forskolin. An alpha(2)M* concentration-dependent rapid increase in phosphorylated CREB at Ser(133) also occurred, a necessary event in its activation. Inhibition of Ca(2+)/calmodulin kinase, protein kinases A and C, tyrosine kinases, ribosomal S6 kinase, farnesyl transferase, extracellular signal-regulated kinases 1/2, phosphatidylinositol 3-kinase, or p38 mitogen-activated protein kinase markedly reduce alpha(2)M*-induced phosphorylation of CREB, indicating a role for the p21(ras)-dependent and phosphatidylinositol 3-kinase signaling pathways in regulating CREB activation by alpha(2)M*. Finally, silencing the CREB gene by transfecting cells with a homologous gene sequence double-stranded RNA drastically reduced the expression of CREB and blocked the ability of alpha(2)M* to promote macrophage cell division. We conclude that cAMP-dependent signal transduction as well as other signaling cascades are essential for alpha(2)M*-induced cell proliferation. |
