title: Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.
abstract: BACKGROUND
  Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK)-Signal transducer and activator of transcription (STAT) pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP), Protein inhibitors against Stats (PIAS), and Suppressor of cytokine signaling (SOCS) proteins across a diverse range of organisms.
  
  
  RESULTS
  Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components.
  
  
  CONCLUSIONS
  Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.
authors.affiliation: School of Medicine, Deakin University, Victoria, Australia.
authors.forename: Clifford
authors.initials: C
authors.lastname: Liongue
authors.forename: Lynda A
authors.initials: LA
authors.lastname: O'Sullivan
authors.forename: Monique C
authors.initials: MC
authors.lastname: Trengove
authors.forename: Alister C
authors.initials: AC
authors.lastname: Ward
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D053612:Janus Kinases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D010802:Phylogeny; D050828:Protein Inhibitors of Activated STAT / Q000145:classification / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000145:classification / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D026801:Synteny
chemical_list: D050828:Protein Inhibitors of Activated STAT; D018160:Receptors, Cytoplasmic and Nuclear; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases