Disease relevance of put

• A Drosophila model of early onset torsion dystonia suggests impairment in TGF-beta signaling [1].

High impact information on put

• TGF-beta signaling activates steroid hormone receptor expression during neuronal remodeling in the Drosophila brain [2].
• In signaling involving the transforming growth factor-beta (TGF-beta) superfamily of proteins, ligand binding brings the constitutively active type II receptor kinase into close proximity to its substrate, the type I receptor kinase, which it then activates by phosphorylation [3].
• Signaling by TGF beta-related factors requires ligand-induced association between type I and type II transmembrane serine/threonine kinases [4].
• Drosophila sequences at chromosomal positions 25D (Brk25D) and 43E (Brk43E) are similar to the TGF beta type I receptor serine/threonine kinases and are expressed broadly during embryogenesis [5].
• The dpp/BMP family of TGF beta-related factors controls numerous events in pattern formation and morphogenesis [6].

Biological context of put

• In this study we describe the role of Baboon (Babo), a type I Activin receptor previously called Atr-I, in Drosophila development and characterize aspects of the Babo intracellular signal-transduction pathway [7].
• The Drosophila activin receptor baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development [7].
• This is consistent with a role for PP1 in antagonizing Punt by preventing phosphorylation of Tkv [8].
• The tight correspondence between both embryonic and postembryonic loss-of-function punt and dpp phenotypes implicates a role for Punt in mediating virtually all Dpp signaling events in Drosophila [9].
• Taken together, these results suggest that the Punt protein functions as a dimer or higher order multimer throughout the Drosophila life cycle [9].

Anatomical context of put

• Dawdle (Daw), a divergent TGF-beta superfamily ligand expressed in glia and mesoderm, is required for embryonic motoneuron pathfinding in Drosophila [10].
• At least half of the Dorsal target genes encode transcription factors or signaling components that lead to the restricted activation of FGF, EGF, and TGF-beta signaling pathways in the mesoderm, neurogenic ectoderm and dorsal ectoderm, respectively [11].
• Maternal Atr-II transcript and its product are abundant in the oocyte [12].
• No other TGF-beta cDNAs have been detected, suggesting that BMP-2 is the major dpp subgroup protein synthesized by HFR endoderm cells [13].
• Smad3, phosphorylated by TGF-beta signalling, interacts with GATA3 to induce differentiation of T helper cells [14].

Associations of put with chemical compounds

• Here we report a genetic characterization of the Drosophila punt gene that encodes a type II serine/threonine kinase TGF-beta/Dpp (Decapentaplegic) receptor [9].
• With the exception of the spacing of 10 cysteine residues, the extracellular domain of Atr-II is very dissimilar from those of vertebrate activin receptors, yet it binds activin with high affinity and specificity [12].
• DTFR has striking homology to mTFR11, especially in the cytoplasmic domain (approx. 63%), including a Ser + Gly-rich box that is characteristic of type-I receptors for the TGF-beta superfamily [15].
• Either attachment of an epitope tag to the C terminus or replacement of these three serine residues with alanine abolishes TGF-beta-induced Smad3 phosphorylation; these proteins act in a dominant-negative fashion to block the antiproliferative effect of TGF-beta in mink lung epithelial cells [16].
• Multiple requirements for the receptor serine/threonine kinase thick veins reveal novel functions of TGF beta homologs during Drosophila embryogenesis [17].

Regulatory relationships of put

• However, Atr-I binds activin efficiently when coexpressed with the distantly related Drosophila activin receptor Atr-II, with which it forms a heteromeric complex [18].

Other interactions of put

• We find that Daw initiates an activin signaling pathway via the receptors Punt and Baboon (Babo) and the signal-transducer Smad2 [10].
• Binding of Decapentaplegic to the putative transforming-growth-factor-beta-like receptors Thickveins and Punt activates a transforming-growth-factor-beta-like pathway that is also required for dorsal closure [19].
• punt and schnurri regulate a somatically derived signal that restricts proliferation of committed progenitors in the germline [20].

Analytical, diagnostic and therapeutic context of put

• Numerous cross-species experiments have shown that TGF-beta family members and their signal transduction machinery (receptors and Smad signal transducers) are functionally conserved between vertebrates and invertebrates [21].
• Immunostaining patterns indicating that HFR endoderm cells express Drosophila decapentaplegic (dpp)-like antigens prompted a degenerate polymerase chain reaction (PCR) screen to identify cDNAs in the dpp subgroup of the transforming growth factor-beta (TGF-beta) family [13].
• Genome-wide microarray analysis of TGFbeta signaling in the Drosophila brain [22].
• In Caenorhabditis elegans, the DBL-1 pathway, a BMP/TGFbeta-related signaling cascade, regulates body size and male tail development [23].
• Northern blot and in situ hybridization studies have demonstrated that CTGF is coordinately expressed with TGF-beta in every fibrotic disorder examined to date [24].

References