Dd-STATb, a<i>Dictyostelium</i>STAT protein with a highly aberrant SH2 domain, functions as a regulator of gene expression during growth and early development

Zhukovskaya, Natasha V.; Fukuzawa, Masashi; Tsujioka, Masatsune; Jermyn, Keith A.; Kawata, Takefumi; Abe, Tomoaki; Zvelebil, Marketa; Williams, Jeffrey

doi:10.1242/dev.00927

Cited by 27 publications

(19 citation statements)

References 38 publications

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“…As implied by the known evolutionary conservation of canonical STAT functions, unphosphorylated vertebrate STATs have also been reported to be associated with chromatin or bound to DNA as either monomers or dimers [25,26]. Consistent with this, low levels of unphosphorylated STAT1 can be found in the nucleus of many cell lines [27], whilst STAT3 shuttles between cytoplasm and nucleus independent of its phosphorylation status [28].…”

Section: Hints From Vertebrates Worms and Slimementioning

confidence: 75%

Unphosphorylated STATs go nuclear

Brown¹,

Zeidler

2008

Current Opinion in Genetics & Development

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Section: Hints From Vertebrates Worms and Slimementioning

confidence: 75%

Unphosphorylated STATs go nuclear

Brown¹,

Zeidler

2008

Current Opinion in Genetics & Development

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“…1b) indicates that these two domains most likely evolved before TyrK domains. In several cases, these non-metazoan SH2 and PTP domains have been experimentally shown to have their traditional biochemical functions, P-Tyr binding and P-Tyr removal, respectively (15). Why would there be a functional advantage to have these reader and eraser domains even in the absence of the TyrK writer domain?…”

Section: Discussionmentioning

confidence: 99%

Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages

Pincus

Letunić²,

Bork³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

157

148

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Multicellular animals use a three-part molecular toolkit to mediate phospho-tyrosine signaling: Tyrosine kinases (TyrK), protein tyrosine phosphatases (PTP), and Src Homology 2 (SH2) domains function, respectively, as ''writers,'' ''erasers,'' and ''readers'' of phospho-tyrosine modifications. How did this system of three components evolve, given their interdependent function? Here, we examine the usage of these components in 41 eukaryotic genomes, including the newly sequenced genome of the choanoflagellate, Monosiga brevicollis, the closest known unicellular relative to metazoans. This analysis indicates that SH2 and PTP domains likely evolved earliest-a handful of these domains are found in premetazoan eukaryotes lacking tyrosine kinases, most likely to deal with limited tyrosine phosphorylation cross-catalyzed by promiscuous Ser/Thr kinases. Modern TyrK proteins, however, are only observed in two lineages, metazoans and choanoflagellates. These two lineages show a dramatic coexpansion of all three domain families. Concurrent expansion of the three domain families is consistent with a stepwise evolutionary model in which preexisting SH2 and PTP domains were of limited utility until the appearance of the TyrK domain in the last common ancestor of metazoans and choanoflagellates. The emergence of the full threecomponent signaling system, with its dramatically increased encoding potential, may have contributed to the advent of metazoan multicellularity.choanoflagellates ͉ encoding potential ͉ tyrosine kinase ͉ src homology 2 ͉ protein tyrosine phosphatase T yrosine phosphorylation is essential for cell-cell communication in animals, mediating hormone, growth factor, immune, and adhesion-based signaling (1-4). Thus, phosphotyrosine (P-Tyr) signaling has traditionally been linked with metazoan multicellularity (5). Metazoan phospho-tyrosine signaling pathways are built from a three-part system of molecular components: Tyrosine kinases (TyrK) are catalytic domains that add phospho-tyrosine (P-Tyr) modifications, protein tyrosine phosphatases (PTP) are catalytic domains that remove these modifications, and Src Homology 2 (SH2) domains are recognition domains that readout these modifications. These modules play the role of ''writer,'' ''eraser,'' and ''reader,'' respectively, a triad of core functions at the heart of many biological and nonbiological information processing systems (6, 7). By using these three modules in combination, remarkably diverse signaling responses can be generated.A fundamentally important question is how this and other biological reader/writer/eraser information processing systems could have initially evolved, given the highly interdependent function of the individual parts in modern organisms. Because they act as a synergistic system, an incomplete set of components would be deficient in function. What selective advantage could have sustained a stepwise evolutionary path?The P-Tyr signaling machinery presents a particularly interesting case, because it appears to have evolved relatively rece...

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“…In Dictyostelium, four STAT genes, DdSTATa, b, c and d, have been identified so far (Kawata et al 1997;Mohanty et al 1999;Fukuzawa et al 2001;Zhukovskaya et al 2004). Dd-STATa is necessary for efficient chemotactic cell movement at the aggregation stage and morphogenesis after the slug stage (Mohanty et al 1999), suggesting that Dd-STATa plays a role in aggregation and multicellular development by regulating chemotactic cell movement.…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix family proteins that are potential targets of Dd-STATa in Dictyostelium discoideum

et al. 2004

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Dd-STATa is a functional Dictyostelium homologue of metazoan STAT (signal transducers and activators of transcription) proteins, which is activated by cAMP and is thereby translocated into the nuclei of anterior tip cells of the prestalk region of the slug. By using in situ hybridization analyses, we found that the SLF308 cDNA clone, which contains the ecmF gene that encodes a putative extracellular matrix protein and is expressed in the anterior tip cells, was greatly down-regulated in the Dd-STATa-null mutant. Disruption of the ecmF gene, however, resulted in almost no phenotypic change. The absence of any obvious mutant phenotype in the ecmF-null mutant could be due to a redundancy of similar genes. In fact, a search of the Dictyostelium whole genome database demonstrates the existence of an additional 16 homologues, all of which contain a cellulose-binding module. Among these homologues, four genes show Dd-STATa-dependent expression, while the others are Dd-STATa-independent. We discuss the potential role of Dd-STATa in morphogenesis via its effect on the interaction between cellulose and these extracellular matrix family proteins.

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Dd-STATb, aDictyosteliumSTAT protein with a highly aberrant SH2 domain, functions as a regulator of gene expression during growth and early development

Cited by 27 publications

References 38 publications

Unphosphorylated STATs go nuclear

Unphosphorylated STATs go nuclear

Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages

Extracellular matrix family proteins that are potential targets of Dd-STATa in Dictyostelium discoideum

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