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Analysis of Thisbe and Pyramus functional domains reveals evidence for cleavage of Drosophila FGFs

Tulin, Sarah and Stathopoulos, Angelike (2010) Analysis of Thisbe and Pyramus functional domains reveals evidence for cleavage of Drosophila FGFs. BMC Developmental Biology, 10 . Art. No. 83. ISSN 1471-213X. PMCID PMC2923630. https://resolver.caltech.edu/CaltechAUTHORS:20101102-104243952

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Abstract

Background: As important regulators of developmental and adult processes in metazoans, Fibroblast Growth Factor (FGF) proteins are potent signaling molecules whose activities must be tightly regulated. FGFs are known to play diverse roles in many processes, including mesoderm induction, branching morphogenesis, organ formation, wound healing and malignant transformation; yet much more remains to be learned about the mechanisms of regulation used to control FGF activity. Results: In this work, we conducted an analysis of the functional domains of two Drosophila proteins, Thisbe (Ths) and Pyramus (Pyr), which share homology with the FGF8 subfamily of ligands in vertebrates. Ths and Pyr proteins are secreted from Drosophila Schneider cells (S2) as smaller N-terminal fragments presumably as a result of intracellular proteolytic cleavage. Cleaved forms of Ths and Pyr can be detected in embryonic extracts as well. The FGF-domain is contained within the secreted ligand portion, and this domain alone is capable of functioning in the embryo when ectopically expressed. Through targeted ectopic expression experiments in which we assay the ability of full-length, truncated, and chimeric proteins to support cell differentiation, we find evidence that (1) the C-terminal domain of Pyr is retained inside the cell and does not seem to be required for receptor activation and (2) the C-terminal domain of Ths is secreted and, while also not required for receptor activation, this domain does plays a role in limiting the activity of Ths when present. Conclusions: We propose that differential protein processing may account for the previously observed inequalities in signaling capabilities between Ths and Pyr. While the regulatory mechanisms are likely complex, studies such as ours conducted in a tractable model system may be able to provide insights into how ligand processing regulates growth factor activity.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1186/1471-213X-10-83DOIArticle
http://www.biomedcentral.com/1471-213X/10/83PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923630/PubMed CentralArticle
ORCID:
AuthorORCID
Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:© 2010 Tulin and Stathopoulos; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 5 March 2010; Accepted: 5 August 2010; Published: 5 August 2010. We thank Leslie Dunipace, Sophie Katz, and Tuomas Brock for excellent technical assistance, Phoebe Tzou for plasmids, the Bloomington Stock Center for fly stocks, Manfred Frasch for the anti-Eve antibody, and the Caltech Protein Expression Facility for protein purification. We are also grateful to Young Bae, Louisa Liberman, and Amy McMahon for comments on the manuscript and to Greg Reeves for help with graphical representations. This work was supported by grant R01 GM078542 to A. S. from the NIH. Authors’ contributions: ST and AS conceived of the study and designed the experiments, which were performed by ST. ST and AS wrote the manuscript. All authors read and approved the final manuscript.
Funders:
Funding AgencyGrant Number
NIHR01 GM078542
PubMed Central ID:PMC2923630
Record Number:CaltechAUTHORS:20101102-104243952
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20101102-104243952
Official Citation:Tulin and Stathopoulos: Analysis of Thisbe and Pyramus functional domains reveals evidence for cleavage of Drosophila FGFs. BMC Developmental Biology 2010 10:83.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:20639
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:02 Nov 2010 18:20
Last Modified:03 Oct 2019 02:13

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