Michael Karin

Bio: Michael Karin is an academic researcher from University of California, San Diego. The author has contributed to research in topics: IκB kinase & Signal transduction. The author has an hindex of 236, co-authored 704 publications receiving 226485 citations. Previous affiliations of Michael Karin include Sanford-Burnham Institute for Medical Research & University of California, Los Angeles.

Cell type specific expression of the growth hormone gene and its control by GHF-1.

Abstract: One of the major challenges in molecular genetics is to determine the mechanisms which control the utilization of genetic information in time and space dependent manners. Differential gene activation is the basis for the processes of cellular differentiation and specialization. Through genetic analysis, a great deal has been learned about the general mechanisms which control these processes in organisms such as D. melanogaster and C . elegans . Although mammals, on the other hand, are refractory to genetic analysis, significant progress has been made in understanding the mechanisms involved in determining tissue specific gene expression in these organisms. This can be mostly attributed to a biochemical approach employing in vitro transcription systems in which differential promoter utilization could be observed, resulting in identification of transcription factors mediating cell-type specific gene expression (Scheidereit et al. 1987; Lichtsteiner et al. 1989; Bodner and Karin 1987) . Several of these factors were purified to homogeneity and their cDNAs were cloned (Bodner et al. 1988; Scheidereit et al. 1988) . In this review we will describe our studies on the control of growth hormone (GH) gene expression. A major emphasis will be placed on the mechanisms responsible for the cell type specific expression of this gene. The GH gene family represents an excellent system for studying the mechanisms responsible for cell type specific gene expression (Karin, 1989) . In addition to GH, this family includes several other genes coding for hormones of physiological and clinical importance, such as prolactin (Prl) and the various placental lactogens (PL) (Miller and Eberhardt, 1983) . GH is specifically expressed in specialized cells, the somatotrophs, of the anterior pituitary. It is required for postnatal growth and maintenance of nitrogen, mineral, lipid and carbohydrate metabolism (Martin, 1973) . Its most important function is probably the stimulation of protein synthesis,

Abstract 93: Sestrin2 Mediates the LKB1-AMPK Signaling Cascade in the Ischemic Heart

Abstract: Background: AMP-activated Protein Kinase (AMPK) has emerged as a pertinent stress-activated kinase shown to have substantial cardioprotective capabilities against myocardial ischemia/reperfusion (I/R) injury. The regulation of AMPK in the ischemic and reperfused heart is critical to the development of new therapeutic strategies. We hypothesized that a novel stress-inducible protein, sestrin2, mediates AMPK activation in the ischemic heart. Methods and Results: C57BL/6 mice were subjected to left anterior descending coronary artery occlusion for different time points of ischemia and I/R in order to detect the signaling activity in the left ventricle. The kinetics of AMPK phosphorylation at Thr 172 of the α catalytic subunit appears brief and bell-shaped, peaking around 10 min (3.6-fold vs. sham, p vs. sham, p 172 ) (10 min), suggesting the interaction of LKB1 with sestrin2 initiates the phosphorylation of AMPK in this complex. Furthermore, sestrin2 knock out hearts demonstrate impaired ischemic AMPK activation and higher sensitivity to I/R-induced injury as compared to wild type hearts ( p Conclusions: Here we show for the first time evidence of a unique mechanism that sestrin2 is a stress-induced scaffold protein that mediates the activation of AMPK in the ischemic myocardium via a time-dependent interaction with LKB1. Moreover, sestrin2 deficiency leads to blunted ischemic AMPK activation and increased sensitivity to ischemic insults.

Gamma subunit of cytokine responsive lkB-alpha kinase complex

Abstract: The present invention provides a novel essential regulatory subunit of the IκB kinase (IKK) complex, IKK-γ. The isolated IKK-γ subunit of the invention has substantially the same amino acid sequence as SEQ ID NO: 2 shown in FIG. 2.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

REACTIVE OXYGEN SPECIES: Metabolism, Oxidative Stress, and Signal Transduction

Abstract: Several reactive oxygen species (ROS) are continuously produced in plants as byproducts of aerobic metabolism. Depending on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and nonenzymatic mechanisms. Whereas plants are surfeited with mechanisms to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully generate ROS as signaling molecules to control various processes including pathogen defense, programmed cell death, and stomatal behavior. This review describes the mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions. New insights into the complexity and roles that ROS play in plants have come from genetic analyses of ROS detoxifying and signaling mutants. Considering recent ROS-induced genome-wide expression analyses, the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.