The long-term goal of this research project is to understand the complex regulatory mechanism of ERK2, a MAP kinase. MAP kinases are important elements of signal transduction pathways initiated by hormones, cytokines, or environmental stress. MAP kinases such as ERK2 are activated after phosphorylation by MAP/ERK kinases (MEKs), which are themselves activated by Ras/Raf proteins following cell stimulation. As such, these enzymes may present useful therapeutic targets. MAP kinases have several interesting properties, including a complex dual phosphorylation regulatory mechanism and a high substrate specificity for hydroxyamino acids that are followed by proline in the target protein's sequence. Few protein kinase systems have been thoroughly investigated and none has crystallographic data for both the inactive and active or phosphorylated forms of the same enzyme.
| Taylor 4th, Clinton A; Juang, Yu-Chi; Earnest, Svetlana et al. (2015) Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK. Biochemistry 54:5063-71 |
| Piala, Alexander T; Humphreys, John M; Goldsmith, Elizabeth J (2014) MAP kinase modules: the excursion model and the steps that count. Biophys J 107:2006-15 |
| Humphreys, John M; Piala, Alexander T; Akella, Radha et al. (2013) Precisely ordered phosphorylation reactions in the p38 mitogen-activated protein (MAP) kinase cascade. J Biol Chem 288:23322-30 |
| Akella, Radha; Min, Xiaoshan; Wu, Qiong et al. (2010) The third conformation of p38? MAP kinase observed in phosphorylated p38? and in solution. Structure 18:1571-8 |
| Lee, Seung-Jae; Cobb, Melanie H; Goldsmith, Elizabeth J (2009) Crystal structure of domain-swapped STE20 OSR1 kinase domain. Protein Sci 18:304-13 |
| Min, Xiaoshan; Akella, Radha; He, Haixia et al. (2009) The structure of the MAP2K MEK6 reveals an autoinhibitory dimer. Structure 17:96-104 |
| Akella, Radha; Moon, Thomas M; Goldsmith, Elizabeth J (2008) Unique MAP Kinase binding sites. Biochim Biophys Acta 1784:48-55 |
| Goldsmith, Elizabeth J; Akella, Radha; Min, Xiaoshan et al. (2007) Substrate and docking interactions in serine/threonine protein kinases. Chem Rev 107:5065-81 |
| Wilsbacher, Julie L; Juang, Yu-Chi; Khokhlatchev, Andrei V et al. (2006) Characterization of mitogen-activated protein kinase (MAPK) dimers. Biochemistry 45:13175-82 |
| Zhou, Tian-Jun; Sun, Li-Guang; Gao, Yan et al. (2006) Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine. Acta Biochim Biophys Sin (Shanghai) 38:385-92 |
Showing the most recent 10 out of 22 publications
