Prokineticin 2 (PK2) binds to prokineticin receptor 1 and prokineticin receptor 2 (PKR1 and PKR2, respectively), two G protein-coupled receptors (GPCRs) that can mediate multiple signalling pathways by promoting the elevation of intracellular calcium and cAMP levels, phosphorylation of Akt and activation of ERK and STAT3. This work aims to evidence the conservation of protein sequence and the mechanism of PK2 binding to PKR1 to use the zebrafish model for the identification of new drugs as targets of prokineticin receptors. To this end, we first demonstrated that the zebrafish genes pk2 and pkr1 are phylogenetically related to orthologous mammalian genes by constructing evolutionary trees and performing syntenic analyses. Subsequently, by comparing the amino acid sequences, we showed that the interaction sites with PK2 are conserved in the zPKR1. Using GST pull- down and cross-linking experiments, we demonstrated the crucial role of the N-terminal region of zPKR1 for binding to the PK2. Finally, by expressing zPKR1 in CHO cells, we demonstrated the ability of zPKR1 to induce the activation of ERK and STAT3.

Biochemical characterization of Prokineticin 2 binding to Prokineticin receptor 1 in zebrafish / Lattanzi, Roberta; Fullone, Maria Rosaria; DE BIASE, Alessio; Maftei, Daniela; Vincenzi, Martina; Miele, Rossella. - In: NEUROPEPTIDES. - ISSN 0143-4179. - 107:(2024), pp. 1-11. [10.1016/j.npep.2024.102456]

Biochemical characterization of Prokineticin 2 binding to Prokineticin receptor 1 in zebrafish

Roberta Lattanzi
Conceptualization
;
Maria Rosaria Fullone
Methodology
;
Alessio De Biase
Methodology
;
Daniela Maftei
Methodology
;
Martina Vincenzi
Methodology
;
Rossella Miele
Writing – Original Draft Preparation
2024

Abstract

Prokineticin 2 (PK2) binds to prokineticin receptor 1 and prokineticin receptor 2 (PKR1 and PKR2, respectively), two G protein-coupled receptors (GPCRs) that can mediate multiple signalling pathways by promoting the elevation of intracellular calcium and cAMP levels, phosphorylation of Akt and activation of ERK and STAT3. This work aims to evidence the conservation of protein sequence and the mechanism of PK2 binding to PKR1 to use the zebrafish model for the identification of new drugs as targets of prokineticin receptors. To this end, we first demonstrated that the zebrafish genes pk2 and pkr1 are phylogenetically related to orthologous mammalian genes by constructing evolutionary trees and performing syntenic analyses. Subsequently, by comparing the amino acid sequences, we showed that the interaction sites with PK2 are conserved in the zPKR1. Using GST pull- down and cross-linking experiments, we demonstrated the crucial role of the N-terminal region of zPKR1 for binding to the PK2. Finally, by expressing zPKR1 in CHO cells, we demonstrated the ability of zPKR1 to induce the activation of ERK and STAT3.
2024
gpcr; zebrafish; prokineticin 2; prokineticin receptor 1
01 Pubblicazione su rivista::01a Articolo in rivista
Biochemical characterization of Prokineticin 2 binding to Prokineticin receptor 1 in zebrafish / Lattanzi, Roberta; Fullone, Maria Rosaria; DE BIASE, Alessio; Maftei, Daniela; Vincenzi, Martina; Miele, Rossella. - In: NEUROPEPTIDES. - ISSN 0143-4179. - 107:(2024), pp. 1-11. [10.1016/j.npep.2024.102456]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1717238
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