Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components.

Savage, Cathy; Das, Pradeep; Finelli, Alyce L.; Townsend, Scott R.; Sun, Ching-Yu; Baird, Scott Everet; Padgett, Richard W.

doi:10.1073/pnas.93.2.790

Cited by 482 publications

(342 citation statements)

References 41 publications

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“…The L3 loop of Smads has drawn attention as a target of inactivating mutations in Drosophila and Caenorhabditis elegans Smad family members (Sekelsky et al 1995;Savage et al 1996). As inferred from the effect of similar mutations in vertebrate Smads, the L3 loop participates in different interactions that are essential for signaling.…”

Section: Discussionmentioning

confidence: 99%

Determinants of specificity in TGF-β signal transduction

Chen¹,

Hata²,

Lo³

et al. 1998

Genes Dev.

344

226

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Signal transduction by the TGF-␤ family involves sets of receptor serine/threonine kinases, Smad proteins that act as receptor substrates, and Smad-associated transcription factors that target specific genes. We have identified discrete structural elements that dictate the selective interactions between receptors and Smads and between Smads and transcription factors in the TGF-␤ and BMP pathways. A cluster of four residues in the L45 loop of the type I receptor kinase domain, and a matching set of two residues in the L3 loop of the Smad carboxy-terminal domain establish the specificity of receptor-Smad interactions. A cluster of residues in the highly exposed ␣-helix 2 of the Smad carboxy-terminal domain specify the interaction with the DNA-binding factor Fast1 and, as a result, the gene responses mediated by the pathway. By establishing specific interactions, these determinants keep the TGF-␤ and BMP pathways segregated from each other. The transforming growth factor ␤ (TGF-␤) family of polypeptide growth factors regulate cell division, differentiation, motility, adhesion, and death in virtually all metazoan tissues

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Section: Discussionmentioning

confidence: 99%

Determinants of specificity in TGF-β signal transduction

Chen¹,

Hata²,

Lo³

et al. 1998

Genes Dev.

344

226

View full text Add to dashboard Cite

show abstract

“…In Caenorhabditis elegans, a conserved BMP signaling pathway, the Sma/Mab pathway, regulates diverse developmental processes including cell/body size, male-tail morphogenesis, dorsoventral cell patterning, immune regulation, and olfactory learning, among others (7)(8)(9)(10). In the C. elegans Sma/Mab pathway, the secreted ligand DBL-1 (decapentaplegic/bone morphogenetic protein-like-1) binds the type II, DAF-4 (dauer formationdefective-4), and type I, SMA-6 (small-6), receptor complex, and DAF-4 phosphorylates SMA-6, which in turn phosphorylates key residues on SMAD (small and mothers against decapentaplegic) proteins, allowing them to accumulate in the nucleus and activate or repress target gene transcription.…”

mentioning

confidence: 99%

BMP signaling requires retromer-dependent recycling of the type I receptor

Gleason

Akintobi²,

Grant³

et al. 2014

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

105

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The transforming growth factor β (TGFβ) superfamily of signaling pathways, including the bone morphogenetic protein (BMP) subfamily of ligands and receptors, controls a myriad of developmental processes across metazoan biology. Transport of the receptors from the plasma membrane to endosomes has been proposed to promote TGFβ signal transduction and shape BMP-signaling gradients throughout development. However, how postendocytic trafficking of BMP receptors contributes to the regulation of signal transduction has remained enigmatic. Here we report that the intracellular domain of Caenorhabditis elegans BMP type I receptor SMA-6 (small-6) binds to the retromer complex, and in retromer mutants, SMA-6 is degraded because of its missorting to lysosomes. Surprisingly, we find that the type II BMP receptor, DAF-4 (dauer formation-defective-4), is retromer-independent and recycles via a distinct pathway mediated by ARF-6 (ADP-ribosylation factor-6). Importantly, we find that loss of retromer blocks BMP signaling in multiple tissues. Taken together, our results indicate a mechanism that separates the type I and type II receptors during receptor recycling, potentially terminating signaling while preserving both receptors for further rounds of activation.endocytosis | receptor trafficking | C. elegans

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“…The receptor complex is composed of the type I receptor kinase SMA-6 and the constitutively phosphorylated type II receptor kinase DAF-4 (Estevez et al, 1993). Upon the binding of DBL-1, the receptor complex mediates the signal and the cytosolic transducer Smads SMA-2, SMA-3 and SMA-4 (Savage et al, 1996). Mutations in all of the components of the DBL-1 pathway mentioned so far cause identical defects, namely, a small body size and male tail defects.…”

Section: Presence Of a Runx And A Cbfb Homolog In C Elegansmentioning

confidence: 99%

“…In C. elegans, at least three TGFb-like signaling pathways have been identified, namely, the DBL-1 pathway, the DAF-7 pathway, and the UNC-129 pathway (Patterson and Padgett, 2000). The DBL-1 pathway is involved in the regulation of body size and male tail development (Savage et al, 1996;Morita et al, 1999;Suzuki et al, 1999). Consequently, this pathway is also called the Sma/Mab pathway.…”

Section: Presence Of a Runx And A Cbfb Homolog In C Elegansmentioning

confidence: 99%

Homologs of RUNX and CBFβ/PEBP2β in C. elegans

2004

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RUNX proteins are evolutionarily well-conserved transcription factors that are involved in essential aspects of the development of metazoan animals ranging from nematodes to humans. Genetic or epigenetic defects in any one of the three RUNX proteins in humans cause severe diseases. Although much is known about the functions and signaling pathways of the RUNX proteins through the use of mammalian systems, there are still gaps in our knowledge with regard to the functions of the RUNX proteins in normal development and disease states. Recently, the nematode Caenorhabditis elegans was revealed to bear one RUNX homolog (RNT-1) and one homolog of the RUNX protein partner CBFb/PEBP2b (BRO-1). The expression patterns and biological functions of RNT-1 and the manner in which it is regulated are all comparable to what has been observed for the mammalian RUNX proteins. Thus, the nematode system is a promising model system for elucidating the functions and regulation of Runt proteins. In addition, it has recently emerged that the RNT-1 protein is involved in a transforming growth factor beta signaling pathway. The bro-1 gene encoding the CBFb homolog is exclusively expressed in the hypodermis, not in the intestine, which indicates that additional tissue-specific cofactors in the intestine might exist. The possible autoregulation of RNT-1 expression by RNT-1/BRO-1 in the hypodermal cells is also discussed.

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Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components.

Cited by 482 publications

References 41 publications

Determinants of specificity in TGF-β signal transduction

Determinants of specificity in TGF-β signal transduction

BMP signaling requires retromer-dependent recycling of the type I receptor

Homologs of RUNX and CBFβ/PEBP2β in C. elegans

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