The western clawed frog Xenopus tropicalis is an important model for vertebrate development that combines experimental advantages of the African clawed frog Xenopus laevis with more tractable genetics. Here we present a draft genome sequence assembly of X. tropicalis. This genome encodes over 20,000 protein-coding genes, including orthologs of at least 1,700 human disease genes. Over a million expressed sequence tags validated the annotation. More than one-third of the genome consists of transposable elements, with unusually prevalent DNA transposons. Like other tetrapods, the genome contains gene deserts enriched for conserved non-coding elements. The genome exhibits remarkable shared synteny with human and chicken over major parts of large chromosomes, broken by lineage-specific chromosome fusions and fissions, mainly in the mammalian lineage.

Recent studies have indicated that serine phosphorylation regulates the activities of STAT1 and STAT3. However, the kinase(s) responsible and the role of serine phosphorylation in STAT function remain unresolved. In the present studies, we examined the growth factor-dependent serine phosphorylation of STAT1 and STAT3. We provide in vitro and in vivo evidence that the ERK family of mitogen-activated protein (MAP) kinases, but not JNK or p38, specifically phosphorylate STAT3 at serine 727 in response to growth factors. Evidence for additional mitogen-regulated serine phosphorylation is also provided. STAT1 is a relatively poor substrate for all MAP kinases tested both in vitro and in vivo. STAT3 serine phosphorylation, not its tyrosine phosphorylation, results in retarded mobility of the STAT3 protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Importantly, serine 727 phosphorylation negatively modulates STAT3 tyrosine phosphorylation, which is required for dimer formation, nuclear translocation, and the DNA binding activity of this transcriptional regulator. Interestingly, the cytokine interleukin-6 also stimulates STAT3 serine phosphorylation, but in contrast to growth factors, this occurs by an ERK-independent process.The JAK/STAT pathways are activated by various cytokines and growth factors such as interleukin-6 (IL-6), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) (reviewed in references 5 and 15). Once these growth factor or cytokine receptors are occupied by their ligands, tyrosine residues in the cytoplasmic domain of the receptors become phosphorylated by cytokine receptor-associated JAK family tyrosine kinases (19,32) or by the growth factor-activated receptor tyrosine kinases (16,26,34). The phosphorylated tyrosine residue, positioned within specific amino acid sequences, provides docking sites for the recruitment of specific STATs via their SH2 domains (13,33). STATs associated with the receptors are consequently phosphorylated at conserved tyrosine residues. This induces the STATs to dimerize via their own SH2 domains (29), translocate into the nucleus, and activate STAT target genes (30). To date, six STAT proteins have been characterized at the molecular level (reviewed in reference 15).EGF and PDGF activate primarily STAT1 and STAT3 (27,28,31,41). STAT1 and STAT3 can form three distinct dimers to activate target genes: STAT1 or STAT3 homodimers and STAT1-STAT3 heterodimers. Although STAT1 and STAT3 are simultaneously activated by various growth factors and cytokines, the results of knockout-mouse experiments suggest a specific role of STAT1 as a target for interferons (10, 21). However, STAT3 is expected to play a broader role. Recent results which show that STAT3 is activated by the expression of Src oncogenes (39) or infection by human T-cell leukemia virus type 1 (22) raise the possibility that STAT3 is involved in tumorigenic cell growth.Mitogen-activated protein (MAP) kinase pathways play important roles in the regulation of cell growth and differe...

Platelet-derived growth factor receptor (PDGF-R) phosphorylation at tyrosines 740/751 and insulin receptor phosphorylation of insulin receptor substrate-1 effects the recruitment and activation of phosphatidylinositol-3-OH kinase (PI(3)K). Changes in PI(3)K activity correlate with cell growth but its downstream signal transducers are unknown. Activation of the 70/85K S6 kinases (pp70S6k) by serine phosphorylation results in 40S ribosomal protein S6 phosphorylation and is important for G1 cell-cycle transition in a variety of cells. Although receptor tyrosine kinases activate the microtubule-associated protein kinase cascade through SH2-/SH3-adaptor proteins, Sos and c-Ras, it is unclear how tyrosine kinases are coupled to the pp70S6k phosphorylation cascade. Here we report that PI(3)K mediates PDGF or insulin receptor signalling to pp70S6k. PI(3)K-mediated activation of pp70S6k is independent of conventional protein kinase C isoforms. Additionally, rapamycin blocks pp70S6k activation by all mitogens, without inhibiting PI(3)K, and acts downstream in this signalling system.