Hu Et Al., 2004, Proc. Natl. Acad. Sci. U.S.A. 101(25): 9369 - FlyBase

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FlyBase in AWS Open Data FlyBase NIH Grant Terminated Previous Next FB2025_05 , released December 11, 2025 Open Close Reference Citation Hu, X., Yagi, Y., Tanji, T., Zhou, S., Ip, Y.T. (2004). Multimerization and interaction of Toll and Spatzle in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 101(25): 9369--9374. FlyBase ID FBrf0179249 Publication Type Research paper Abstract The Toll family of receptors is required for innate immune response to pathogen-associated molecules, but the mechanism of signaling is not entirely clear. In Drosophila the prototypic Toll regulates both embryonic development and adult immune response. We demonstrate here that the host protein Spätzle can function as a ligand for Toll because Spätzle forms a complex with Toll in transgenic fly extracts and stimulates the expression of a Toll-dependent immunity gene, drosomycin, in adult flies. We also show that constitutively active mutants of Toll form multimers that contain intermolecular disulfide linkages. These disulfide linkages are critical for the activity of one of these mutant receptors, indicating that multimerization is essential for the constitutive activity. Furthermore, systematic mutational analysis revealed that a conserved cysteine-containing motif, different from the cysteines used for the intermolecular disulfide linkages, serves as a self-inhibitory module of Toll. Deleting or mutating this cysteine-containing motif leads to constitutive activity. This motif is located just outside the transmembrane domain and may provide a structural hindrance for multimerization and activation of Toll. Together, our results suggest that multimerization may be a regulated, essential step for Toll-receptor activation. PubMed ID 15197269 PubMed Central ID PMC438983 (PMC) (EuropePMC) DOI 10.1073/pnas.0307062101 Associated Information Comments Associated Files Other Information Secondary IDs Language of Publication English Additional Languages of Abstract Parent Publication Publication Type Journal Abbreviation Proc. Natl. Acad. Sci. U.S.A. Title Proceedings of the National Academy of Sciences of the United States of America Publication Year 1915- ISBN/ISSN 0027-8424 Data From Reference Alleles (17) Export to HitList

• Scer\GAL4Act5C.PU
• Scer\GAL4yolk
• spzΔN.UAS.Tag:MYC
• spzΔN.UAS.Tag:V5
• spzUAS.Tag:MYC
• spzUAS.Tag:V5
• Tl10b.UAS.Tag:FLAG
• Tl10b.UAS.Tag:MYC
• Tl10b
• TlC755Y.C781Y.C799Y.UAS
• TlC755Y.C781Y.UAS
• TlC781S.UAS
• TlC781Y.UAS
• TlUAS.cHa
• TlUAS.Tag:FLAG
• TlUAS.Tag:MYC
• w+mC

Gene Groups (1) Export to HitList

• TOLL-NF-kappaB SIGNALING PATHWAY CORE COMPONENTS

Genes (6) Export to HitList

• Drs
• Ppyr\LUC
• Scer\GAL4
• spz
• Tl
• w

Physical Interactions (6) Export to HitList

• spz
• Tl - spz
• Tl

Cell Lines (1) Export to HitList

• S2-unspecified

Experimental Tools (4) Export to HitList

• Tag:FLAG
• Tag:MYC
• Tag:V5
• UAS

Transgenic Constructs (14) Export to HitList

• P{UAS-spz.ΔNMyc}
• P{UAS-spz.ΔNV5}
• P{UAS-spz.Myc}
• P{UAS-spz.V5}
• P{UAS-Tl.10b.FLAG}
• P{UAS-Tl.10b.Myc}
• P{UAS-Tl.C755Y.C781Y.C799Y}
• P{UAS-Tl.C755Y.C781Y}
• P{UAS-Tl.C781S}
• P{UAS-Tl.C781Y}
• P{UAS-Tl.FLAG}
• P{UAS-Tl.H}
• P{UAS-Tl.Myc}
• P{yolk-GAL4}

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