Evolution of Class I cytokine receptors

Liongue, Clifford; Ward, Alister C.

doi:10.1186/1471-2148-7-120

Cited by 136 publications

(163 citation statements)

References 47 publications

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“…This was also the case for class 1 and class 2 cytokines and their receptors 90,91 . Given their physiological and physical interaction, it will be interesting to assess whether cytokine and TAM receptors may have co-evolved.…”

Section: Box 2 | Primordial Tam Receptors and Ligandssupporting

confidence: 52%

Immunobiology of the TAM receptors

2008

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Recent studies have revealed that the TAM receptor protein tyrosine kinases -TYRO3, AXL and MER -have pivotal roles in innate immunity. They inhibit inflammation in dendritic cells and macrophages, promote the phagocytosis of apoptotic cells and membranous organelles, and stimulate the maturation of natural killer cells. Each of these phenomena may depend on a cooperative interaction between TAM receptor and cytokine receptor signalling systems. Although its importance was previously unrecognized, TAM signalling promises to have an increasingly prominent role in studies of innate immune regulation.Receptor protein tyrosine kinases (PTKs) are cell-surface transmembrane receptors that contain a regulated PTK activity within their cytoplasmic domains. They function as sensors for extracellular ligands, the binding of which triggers receptor dimerization and activation of the receptor's kinase. This leads to the recruitment, phosphorylation and activation of multiple downstream signalling proteins, which ultimately change the physiology of cells. Although there are only 58 receptor PTK genes in the human genome 1 (see the human kinome website), the signal transduction cascades initiated by receptor PTK activation control diverse cellular processes -from cell differentiation to cell death. Well-known receptor PTK subfamilies include the ERBB receptors, which have essential roles in cardiac and neural development and the progression of some forms of breast cancer 2 ; and the ephrin receptors, which are required for tissue morphogenesis and the patterning of neuronal connections in the developing brain 3 .The focus of this Review, the TAM group, was among the last receptor PTK subfamilies to be identified, and the biological roles of its three members -TYRO3, AXL and MERremained uncharacterized for several years. Largely through the analysis of engineered lossof-function mutants in mice, these roles have become increasingly apparent. They reflect a specific requirement for TAM signalling in settings in which fully differentiated cells, tissues and organs must be maintained in the face of continuous challenge, turnover and renewal. In humans, ongoing homeostatic regulation of this sort must be carried out, frequently on a daily basis, for decades. Although an essential role for TAM regulation of tissue homeostasis is evident in the adult nervous, reproductive and vascular systems, it is in In this Review, we highlight the central roles that TAM signalling has in the intrinsic inhibition of the inflammatory response to pathogens by dendritic cells (DCs) and macrophages; during phagocytosis of apoptotic cells by these same cells; and in the maturation and killing activity of natural killer (NK) cells. We also discuss how, in many or all of these settings, TAM receptors depend on and interact with cytokine receptors. TAM receptors and ligandsThe three TAM receptors, TYRO3, AXL and MER, were identified as a distinct receptor PTK subfamily in 1991 (REFS 4,5 ). Subsequent cloning of full-length cDNAs by multiple labo...

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Section: Box 2 | Primordial Tam Receptors and Ligandssupporting

confidence: 52%

Immunobiology of the TAM receptors

2008

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“…This is due to the lack of informative mutants, incomplete information concerning the complexity of the cytokine gene families, and the paucity of suitable in vitro assay systems. With regard to IL-7 signaling, genes encoding homologs of IL-7Ra, TSLPR, and g c chains (24) as well as those encoding the receptor-proximal JAKs have been detected in fish (25). By contrast, it is often difficult to make an unambiguous assignment of presumptive g c cytokines by homology search in genome and expressed sequence tag databases available for lower vertebrates (26), because the primary amino acid sequences of ILs appear to be poorly conserved.…”

mentioning

confidence: 99%

Genetic Evidence for an Evolutionarily Conserved Role of IL-7 Signaling in T Cell Development of Zebrafish

Iwanami

Mateos

Hess

et al. 2011

The Journal of Immunology

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In mammals, the cytokine IL-7 is a key regulator of various aspects of lymphocyte differentiation and homeostasis. Because of the difficulty of identifying cytokine homologs in lower vertebrates and the paucity of assay systems and reagents, the degree of functional conservation of cytokine signaling pathways, particularly those pertaining to lymphocyte development, is unclear. In this article, we report on the analysis and characterization of three zebrafish mutants with severely impaired thymopoiesis. The identification of affected genes by positional cloning revealed components of the IL-7 signaling pathway. A presumptive null allele of the zebrafish homolog of the IL-7Rα–chain causes substantially reduced cellularity of the thymus but spares B cell development in the kidney. Likewise, nonsense mutations in the zebrafish homologs of janus kinases JAK1 and JAK3 preferentially affect T cell development. The functional interactions of the cytokine receptor components were examined in the three groups of fish hetero- or homozygous for either il7r and jak1, il7r and jak3, or jak1 and jak3 mutations. The differential effects on T cell development arising from the different genotypes could be explained on the basis of the known structure of the mammalian IL-7R complex. Because IL-7 signaling appears to be a universal requirement for T cell development in vertebrates, the mutants described in this article represent alternative animal models of human immunodeficiency syndromes amenable to large-scale genetic and chemical screens.

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“…interleukins; Huising et al 2006). All class-I helical cytokines fold in a typical four a-helix barrel structure and signal through a group of related receptors (Liongue & Ward 2007). These cytokines activate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, ultimately leading to changes in gene expression.…”

Section: Introductionmentioning

confidence: 99%

STAT genes display differential evolutionary rates that correlate with their roles in the endocrine and immune system

Gorissen¹,

Vrieze²,

Flik³

et al. 2011

Journal of Endocrinology

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We identified orthologues of all mammalian Janus kinase (JAK) and signal transducer and activator of transcription (STAT) genes in teleostean fishes, indicating that these protein families were already largely complete before the teleost tetrapod split, 450 million years ago. In mammals, the STAT repertoire consists of seven genes (STAT1, -2, -3, -4, -5a, -5b, and -6). Our phylogenetic analyses show that STAT proteins that are recruited downstream of endocrine hormones (STAT3 and STAT5a and -5b) show a markedly higher primary sequence conservation compared with STATs that convey immune signals (STAT1-2, STAT4, and STAT6).A similar dichotomy in evolutionary conservation is observed for the JAK family of protein kinases, which activate STATs. The ligands to activate the JAK/STAT-signalling pathway include hormones and cytokines such as GH, prolactin, interleukin 6 (IL6) and IL12. In this paper, we examine the evolutionary forces that have acted on JAK/STAT signalling in the endocrine and immune systems and discuss the reasons why the JAK/STAT cascade that conveys classical immune signals has diverged much faster compared with endocrine JAK/STAT paralogues.

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Evolution of Class I cytokine receptors

Cited by 136 publications

References 47 publications

Immunobiology of the TAM receptors

Immunobiology of the TAM receptors

Genetic Evidence for an Evolutionarily Conserved Role of IL-7 Signaling in T Cell Development of Zebrafish

STAT genes display differential evolutionary rates that correlate with their roles in the endocrine and immune system

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