Cells communicate using a relatively small number of signaling pathways, including the TGF-β/BMP pathway. Transmembrane receptors play a central role in signal transduction because they directly convert information outside of the cell into molecular changes inside the cell. My research in the O'Connor lab has uncovered several novel properties of TGF-β receptors in the fruit fly. The Baboon receptor typically signals through the dSmad2 transcription factor. We found that information also flows in the reverse direction, such that the availability of the preferred substrate controls other activities of the receptor. If dSmad2 is unavailable, Baboon will activate Mad, an evolutionary cousin of dSmad2. Stimulation of dSmad2 leads to its degradation, generating a potential temporal substrate switching mechanism. Baboon behaves badly in other ways when dSmad2 is removed, leading to severe defects in tissue growth. I continue to study these signaling configurations to learn how they are deployed in development, and to model unexpected outcomes of TGF-β signaling defects in human diseases.
Another aspect of receptor behavior that can limit signaling events is the restricted localization of the receptors to specific membrane domains. In collaboration with the Leof lab at the Mayo Clinic, I discovered that two Type II receptors are targeted to different membrane locations and identified a novel basolateral targeting motif. An ongoing project in the lab is identifying the cell biological mechanism of receptor trafficking, and how the different localization properties spatially restrict signaling to support tissue patterning.
Selected Publications (Pubmed Search)
Peterson AJ, O'Connor MB. Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements. Development. 2013 Feb;140(3):649-59
Peterson, A.J., Jensen, P.A., Shimell, M.J., Stefancsik, R., Wijayatonge, R.,Herder, R. Raftery, L.A. and O'Connor M. B., R-Smad competition controls Activin receptor output inDrosophila. Plos One 7(5): e36548. doi:10.1371/journal.pone.0036548
Peterson, A.J. and O’Connor M.B. (2012) You’re going to need a bigger (glass bottom) boat Science Signaling 5(218) pe14 PMID: 22472647
Peterson AJ, Kossenkov AV, Ochs MF (2007). Linking gene expression patterns and transcriptional control in Plasmodium falciparum. In Methods of Microarray Data Analysis V. McConnell P, Lim SM, Hurban P (eds), Springer US.
Kossenkov AV, Peterson AJ, Ochs MF (2007). Determining transcription factor activity from microarray data using Bayesian Markov chain Monte Carlo sampling. Medinfo. 12(Part 2):1250-4.
Ochs MF, Peterson AJ, Kossenkov A, Bidaut G (2007). Incorporation of Gene Ontology annotations to enhance microarray data analysis. In Microarray Data Analysis: Methods and Applications. Korenberg MJ (ed), Humana Press.
Peterson AJ, Mallin DR, Francis NJ, Ketel CS, Stamm J, Voeller RK, Kingston RE, Simon JA (2004). Requirement for Sex comb on midleg protein interactions in Drosophila Polycomb group repression. Genetics 167:1225-39.
Shimell MJ, Peterson AJ, Burr J, Simon J,O'Connor MB (2000). Functional analysis of repressor binding sites within the iab-2 regulatory region of the abdominal-A homeotic gene. Dev Biol 218:38-52.