Signal transduction and the plasminogen activator system
The plasminogen activator (PA) system plays an important role in processes involving extracellular proteolysis, such as angiogenesis, wound healing, gametogenesis, inflammation and tumor metastasis.
Recent results show a new form of biological regulation by the PA system not involving proteolytic activity in which urokinase-type PA (uPA)-occupied uPA receptor acquires a high affinity for vitronectin, promoting cell adhesion or migration on vitronectin-containing extracellular matrix. Studying regulation of uPA and PA inhibitor-1 by growth factors, we found serine/threonine phosphorylation of the adaptor/docking protein ShcA. Tyrosine phosphorylation of ShcA and its role in signaling have been well documented, but its serine/threonine phosphorylation has been little studied. Our work has revealed a role for serine phosphorylation of ShcA in insulin induced signaling.
Faisal A, Kleiner S, Nagamine Y (2004) Non-redundant role of Shc in Erk activation by cytoskeletal reorganizationJ Biol Chem 279:3202-3211
Tran H, Schilling M, Wirbelauer C, Hess D, Nagamine Y (2004) Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAUMol Cell 13:101-111
Venugopal J, Hanashiro K, Yang ZZ, Nagamine Y (2004) Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytesProc Nat Acad Sci USA 101:17120-17125
Lopez-Alemany R, Redondo J M, Nagamine Y, Munoz-Canoves P (2003) Plasminogen activator inhibitor type-1 inhibits insulin signaling by competing with avbeta3 integrin for vitronectin bindingEur J Biochem 270:814-821
Tran H, Maurer F, Nagamine Y (2003) Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2Mol Cell.Biol 23:7177-7188
Faisal F, El-Shemerly M, Hess D, Nagamine Y (2002) Serine/threonine phosphorylation of ShcA: regulation of PTP-PEST binding and involvement in insulin signalingJ Biol Chem 277:30144-30152
Kisielow M, Kleiner S, Nagasawa M, Faisal A, Nagamine Y (2002) Isoform-specific knock-down and expression of adaptor protein ShcA using small interfering RNABiochem J 363:1-5