Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling

The suppressor of cytokine signaling (SOCS) family of proteins were named after their defining role as negative feedback regulators of signaling initiated by numerous cytokine receptors. However, multiple members of the SOCS family likely function outside of this paradigm, including SOCS4. Zebrafish...

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Main Authors: Monique Trengove, Parisa Rasighaemi, Clifford Liongue, Alister C. Ward
Format: Article
Language:English
Published: MDPI AG 2024-08-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/9/1063
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author Monique Trengove
Parisa Rasighaemi
Clifford Liongue
Alister C. Ward
author_facet Monique Trengove
Parisa Rasighaemi
Clifford Liongue
Alister C. Ward
author_sort Monique Trengove
collection DOAJ
description The suppressor of cytokine signaling (SOCS) family of proteins were named after their defining role as negative feedback regulators of signaling initiated by numerous cytokine receptors. However, multiple members of the SOCS family likely function outside of this paradigm, including SOCS4. Zebrafish possess two <i>SOCS4</i> paralogues, with <i>socs4a</i> previously shown to participate in central nervous system development and function. This study examined the role of the other paralogue, <i>socs4b</i>, through expression analysis and functional investigations in vivo and in vitro. This revealed maternal deposition of <i>socs4b</i> mRNA, specific zygotic expression during late embryogenesis, including in the brain, eye and intestine, and broad adult expression that was highest in the brain. A mutant allele, <i>socs4bΔ18</i>, was generated by genome editing, in which the start codon was deleted. Fish homozygous for this likely hypomorphic allele showed no overt developmental phenotypes. However, in vitro studies suggested the Socs4b protein may be able to regulate EGFR signaling.
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spelling doaj-art-adf0f106a46e42e8bf25c9e1ccde13912025-08-20T01:56:00ZengMDPI AGBiomolecules2218-273X2024-08-01149106310.3390/biom14091063Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor SignalingMonique Trengove0Parisa Rasighaemi1Clifford Liongue2Alister C. Ward3School of Medicine, Deakin University, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Geelong, VIC 3216, AustraliaThe suppressor of cytokine signaling (SOCS) family of proteins were named after their defining role as negative feedback regulators of signaling initiated by numerous cytokine receptors. However, multiple members of the SOCS family likely function outside of this paradigm, including SOCS4. Zebrafish possess two <i>SOCS4</i> paralogues, with <i>socs4a</i> previously shown to participate in central nervous system development and function. This study examined the role of the other paralogue, <i>socs4b</i>, through expression analysis and functional investigations in vivo and in vitro. This revealed maternal deposition of <i>socs4b</i> mRNA, specific zygotic expression during late embryogenesis, including in the brain, eye and intestine, and broad adult expression that was highest in the brain. A mutant allele, <i>socs4bΔ18</i>, was generated by genome editing, in which the start codon was deleted. Fish homozygous for this likely hypomorphic allele showed no overt developmental phenotypes. However, in vitro studies suggested the Socs4b protein may be able to regulate EGFR signaling.https://www.mdpi.com/2218-273X/14/9/1063cytokineEGFRSOCSSOCS4
spellingShingle Monique Trengove
Parisa Rasighaemi
Clifford Liongue
Alister C. Ward
Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling
Biomolecules
cytokine
EGFR
SOCS
SOCS4
title Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling
title_full Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling
title_fullStr Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling
title_full_unstemmed Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling
title_short Zebrafish Suppressor of Cytokine Signaling 4b (Socs4b) Is Dispensable for Development but May Regulate Epidermal Growth Factor Receptor Signaling
title_sort zebrafish suppressor of cytokine signaling 4b socs4b is dispensable for development but may regulate epidermal growth factor receptor signaling
topic cytokine
EGFR
SOCS
SOCS4
url https://www.mdpi.com/2218-273X/14/9/1063
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AT cliffordliongue zebrafishsuppressorofcytokinesignaling4bsocs4bisdispensablefordevelopmentbutmayregulateepidermalgrowthfactorreceptorsignaling
AT alistercward zebrafishsuppressorofcytokinesignaling4bsocs4bisdispensablefordevelopmentbutmayregulateepidermalgrowthfactorreceptorsignaling