Tearina Chu | PubMed Health

PubMed2006

Two dual specificity kinases are preferentially induced by wild-type rather than by oncogenic RAS-P21 in Xenopus oocytes.

In prior studies, we have found that oncogenic ras-p21 protein induces oocyte maturation using pathways that differ from those activated by insulin-induced wild-type ras-p21. Both oncogenic and wild-type ras-p21 require interactions with raf, but unlike oncogenic ras-p21, insulin-activated wild-type ras-p21 does not depend completely on activation of MEK and MAP kinase (MAPK or ERK) on the raf kinase pathway. To determine what raf-dependent but MAPK-independent pathway is activated by wild-type ras-p21, we have analyzed gene expression in oocytes induced to mature either with oncogenic ras-p21 or with insulin using a newly available Xenopus gene array. We find a number of proteins that are preferentially expressed in one or the other system. Of these, two proteins, both dual function kinases, T-Cell Origin Protein Kinase (TOPK) and the nuclear kinase, DYRK1A, are preferentially expressed in the insulin system. Confirming this finding, blots of lysates of oocytes, induced to mature with oncogenic ras-p21 and insulin, with anti-TOPK and anti-DYRK1A show much higher protein expression in the lysates from the insulin-matured oocytes. Neither of these kinases activates or is activated by MAPK and is therefore an attractive candidate for being on a signal transduction pathway that is unique to insulin-activated wild-type ras-p21-induced oocyte maturation.

Animals↗

PubMed2004

Gene expression pattern in hepatic stem/progenitor cells during rat fetal development using complementary DNA microarrays.

To identify new and differentially expressed genes in rat fetal liver epithelial stem/progenitor cells during their proliferation, lineage commitment, and differentiation, we used a high throughput method-mouse complementary DNA (cDNA) microarrays-for analysis of gene expression. The gene expression pattern of rat hepatic cells was studied during their differentiation in vivo: from embryonic day (ED) 13 until adulthood. The differentially regulated genes were grouped into two clusters: a cluster of up-regulated genes comprised of 281 clones and a cluster of down-regulated genes comprised of 230 members. The expression of the latter increased abruptly between ED 16 and ED 17. Many of the overexpressed genes from the first cluster fall into distinct, differentially expressed functional groups: genes related to development, morphogenesis, and differentiation; calcium- and phospholipid-binding proteins and signal transducers; and cell adhesion, migration, and matrix proteins. Several other functional groups of genes that are initially down-regulated, then increase during development, also emerged: genes related to inflammation, blood coagulation, detoxification, serum proteins, amino acids, lipids, and carbohydrate metabolism. Twenty-eight genes overexpressed in fetal liver that were not detected in adult liver are suggested as potential markers for identification of liver progenitor cells. In conclusion, our data show that the gene expression program of fetal hepatoblasts differs profoundly from that of adult hepatocytes and that it is regulated in a specific manner with a major switch at ED 16 to 17, marking a dramatic change in the gene expression program during the transition of fetal liver progenitor cells from an undifferentiated to a differentiated state. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Aging↗