STATs (signal transducers and activators of transcription) are a family of latent cytoplasmic proteins that are activated to participate in gene control when cells encounter various extracellular polypeptides. Biochemical and molecular genetic explorations have defined a single tyrosine phosphorylation site and, in a dimeric partner molecule, an Src homology 2 (SH2) phosphotyrosine-binding domain, a DNA interaction domain, and a number of protein-protein interaction domains (with receptors, other transcription factors, the transcription machinery, and perhaps a tyrosine phosphatase). Mouse genetics experiments have defined crucial roles for each known mammalian STAT. The discovery of a STAT in Drosophila , and most recently in Dictyostelium discoideum , implies an ancient evolutionary origin for this dual-function set of proteins.

http://science.sciencemag.org/content/sci/277/5332/1630.full.pdf

STATs and Gene Regulation

The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation. The first-AUG rule is not absolute, but there are rules for breaking the rule. Some anomalous observations that seemed to contradict the scanning mechanism now appear to be artifacts. A few genuine anomalies remain unexplained.

/pdf/the-scanning-model-for-translation-an-update-52r2in8l71.pdf

The scanning model for translation: an update.

World wheat grain yields increased substantially in the 1960s and 1970s because farmers rapidly adopted the new varieties and cultivation methods of the so-called 'green revolution'. The new varieties are shorter, increase grain yield at the expense of straw biomass, and are more resistant to damage by wind and rain. These wheats are short because they respond abnormally to the plant growth hormone gibberellin. This reduced response to gibberellin is conferred by mutant dwarfing alleles at one of two Reduced height-1 (Rht-B1 and Rht-D1) loci. Here we show that Rht-B1/Rht-D1 and maize dwarf-8 (d8) are orthologues of the Arabidopsis Gibberellin Insensitive (GAI) gene. These genes encode proteins that resemble nuclear transcription factors and contain an SH2-like domain, indicating that phosphotyrosine may participate in gibberellin signalling. Six different orthologous dwarfing mutant alleles encode proteins that are altered in a conserved amino-terminal gibberellin signalling domain. Transgenic rice plants containing a mutant GAI allele give reduced responses to gibberellin and are dwarfed, indicating that mutant GAI orthologues could be used to increase yield in a wide range of crop species.

‘Green revolution’ genes encode mutant gibberellin response modulators

Cytokines and interferons are molecules that play central roles in the regulation of a wide array of cellular functions in the lympho-hematopoietic system. These factors stimulate proliferation, differentiation, and survival signals, as well as specialized functions in host resistance to pathogens. Although cytokines are known to activate multiple signaling pathways that together mediate these important functions, one of these pathways, the Jak-STAT pathway, is the focus of this chapter. This pathway is triggered by both cytokines and interferons, and it very rapidly allows the transduction of an extracellular signal into the nucleus. The pathway uses a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosine kinases (Jaks), allowing STAT protein dimerization and nuclear translocation. STATs then can modulate the expression of target genes. The basic biology of this system, including the range of known Jaks and STATs, is discussed, as are the defects in animals and humans lacking some of these signaling molecules.

/pdf/jaks-and-stats-biological-implications-23mq0jx75j.pdf

JAKS AND STATS: Biological Implications*

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

/pdf/the-genome-of-the-social-amoeba-dictyostelium-discoideum-3gwppfdmpl.pdf

The genome of the social amoeba Dictyostelium discoideum

https://www.cell.com/cell/pdf/S0092-8674(00)80276-7.pdf

SH2 Signaling in a Lower Eukaryote: A STAT Protein That Regulates Stalk Cell Differentiation in Dictyostelium

https://www.cell.com/cell/pdf/0092-8674(87)90559-9.pdf

Direct induction of dictyostelium prestalk gene expression by DIF provides evidence that DIF is a morphogen

The characteristic structure of the mature Dictyostelium culminant is created by the regionalized cellular differentiation and directed movement of prestalk cells. The front prestalk zone of the migratory slug has previously been considered to be a homogeneous tissue. Here we demonstrate, however, the existence of multiple classes of prestalk cells located in different parts or the slug anterior. The pDd56 and pDd63 genes encoding closely related extracellular matrix proteins are dependent for their expression upon DIF-1, the specific stalk-cell inducer. We have fused the promoters of the two genes to a modified chloramphenicol acetyltransferase (cat) gene to produce immunologically detectable proteins which localize to the cell nucleus. These two markers define three distinct kinds of 'prestalk' cells. One class, which we term 'prestalk A' cells, expressed the pDd63 gene. 'Prestalk B' cells express pDd56 and may also express the pDd63 gene. A third class, which we term 'prestalk 0' cells, expresses neither marker.

A new anatomy of the prestalk zone in Dictyostelium.

Origins of the prestalk-prespore pattern in Dictyostelium development.

We have isolated cDNA clones derived from three mRNA sequences which are inducible by DIF, the putative stalk-specific morphogen of Dictyostelium. The three mRNA sequences are selectively expressed in cells on the stalk cell pathway of differentiation and we have compared them with previously characterized prestalk-enriched mRNA sequences. We find these latter sequences are expressed without a dependence on DIF, are much less highly enriched in prestalk over prespore cells and are expressed earlier during development than the DIF-inducible mRNA sequences. We propose two distinct mechanisms whereby a mRNA may become enriched in prestalk cells. An apparently small number of genes, represented by those we have isolated, is inducible by DIF and accumulates only in prestalk cells. We suggest that a second class of prestalk-enriched mRNA sequences are induced by cAMP to accumulate in all cells during aggregation and then become enriched in prestalk cells by selective loss from prespore cells.

Jeffrey G. Williams

Papers

SH2 Signaling in a Lower Eukaryote: A STAT Protein That Regulates Stalk Cell Differentiation in Dictyostelium

Direct induction of dictyostelium prestalk gene expression by DIF provides evidence that DIF is a morphogen

A new anatomy of the prestalk zone in Dictyostelium.

Origins of the prestalk-prespore pattern in Dictyostelium development.

Two distinct classes of prestalk-enriched mRNA sequences in Dictyostelium discoideum.