Abstract

Suppressor of cytokine signaling 1 (SOCS1) protein can inhibit the signal transduction triggered by some cytokines or hormones and thus are important in many physiological/pathological processes, including innate and adaptive immunity, inflammation, and deve- lopment in mammals. However, there is sparse informa- tion about their structure, tissue expression, in birds, where their biological functions remain unknown. In this study, we cloned and characterized two SOCS1 genes (named cSOCS1a and cSOCS1b) from chickens. SOCS1a is predicted to encode a 207-amino acid protein, which shares high amino acid sequence identity (64%-67%) with human and mouse SOCS1. Besides SOCS1a, a novel SOCS1b gene was also identified in chickens and other non-mammalian vertebrates including Xenopus tropicalis. Chicken SOCS1b is predicted to encode a 212-amino acid protein, which shares only 30%-32% amino acid sequence identity with human SOCS1 and cSOCS1a. RT-PCR assay revealed that both cSOCS1a and cSOCS1b are widely expressed in all chicken tissues. Using a luciferase reporter assay system, we further demonstrated that transient expression of cSOCS1a and cSOCS1b can significantly inhibit chicken growth hormone (GH)- or prolactin (PRL)- induced luciferase activities of Hep G2 cells expressing cGH receptor (or cPRL receptor), indicating that SOCS1a and SOCS1b proteins can negatively regulate GH/PRL signaling. Taken together, these data suggest that both cSOCS1a and cSOCS1b may function as negative regulators of cytokine/hormone actions, such as modula- tion of GH/PRL actions in chickens.

Highlights

  • Suppressor of cytokine signaling (SOCS) proteins are a family of intracellular molecules that can inhibit the signal transduction of many cytokines, growth factors, and hormones[1]

  • The central SRC-homology 2 (SH2) domain and N-terminal region have been shown to be important for binding to Janus kinase (JAK) and inhibiting the signal transduction[6], while the SOCS box can interact with elongin B, elongin C, cullin 5 and RING box 2 (RBX2), and mediate proteasomal degradation of the associated signaling complex[9,10]

  • This novel Suppressor of cytokine signaling 1 (SOCS1)-like gene is designated as the chicken SOCS1b in this study, whereas the abovementioned chicken SOCS1 orthologous to human SOCS1 is defined as the SOCS1a gene

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Summary

Introduction

Suppressor of cytokine signaling (SOCS) proteins are a family of intracellular molecules that can inhibit the signal transduction of many cytokines, growth factors, and hormones[1]. SOCS1 was discovered independently by three laboratories in 1997 and proved to be responsible for the negative regulation of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway triggered by cytokines, growth factors and hormones[1,3,4,5]. As one of the most important negative regulators of cytokine signaling, SOCS1 is reported to be important in many physiological/pathological processes in mammals, such as innate and adaptive immunity, inflammation, hepatitis-induced carcinogenesis, myeloid leukemia, and metabolism syndromes[2,11]. SOCS1 has been reported to inhibit the JAK-STAT signaling pathway activated by growth hormone and prolactin[15,16], the two peptide hormones mainly produced by the vertebrate anterior

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