The year 2003 marks the tenth anniversary of the first use of the acronym "Stat" (also written "STAT") in the scientific literature for a family of transcription factors which rapidly transduce cytokine-and growth factor elicited signals from the plasma membrane to the cell nucleus thereby activating gene transcription (thus, . s. ignal Transducers and Activators of Transcription). From those beginnings, the field of STAT transcription factors, their related regulatory molecules and their biology has grown exponentially in many different directions. In recognition of the rapid growth and broad…mehr
The year 2003 marks the tenth anniversary of the first use of the acronym "Stat" (also written "STAT") in the scientific literature for a family of transcription factors which rapidly transduce cytokine-and growth factor elicited signals from the plasma membrane to the cell nucleus thereby activating gene transcription (thus, . s. ignal Transducers and Activators of Transcription). From those beginnings, the field of STAT transcription factors, their related regulatory molecules and their biology has grown exponentially in many different directions. In recognition of the rapid growth and broad scope of the STAT transcription factor field today, and to celebrate the tenth anniversary of the use of this term in the scientific literature, Kluwer Academic Publishers B. V. requested us to compile a volume on STAT transcription factors that could serve as an overview of this burgeoning area. Thus, we wanted a volume that would serve as a reference for what is known about STAT proteins and their biology, would describe the current state of ongoing research in this broad area, and would look toward the future to try to predict the discoveries that lie ahead. Our charge was to seek out the very best experts in the field and to coax them to briefly summarize their areas of expertise.
1. Introduction: a brief history of the STATs and a glance at the future.- Section I Stat Proteins and Their Regulators.- 2. The STAT protein family.- 3. The Janus kinase protein family.- 4. Structural bases of receptor-JAK-STAT interactions.- 5. SOCS proteins: negative regulators of the JAK/STAT pathway.- 6. The PIAS protein family and TC-PTP.- 7. Prime time for the Drosophila JAK/STAT pathway.- 8. The STAT proteins of Dictyostelium.- 9. JAK/STATs in zebrafish: conservation of JAK/STAT signaling in vertebrates.- Section II Mechanisms of Activation of and Transcriptional Regulation by Stat Proteins.- 10. IFNs and STATs, an incestuous relationship.- 11. Mechanisms and biological roles of STAT activation by the IL-6 family of cytokines.- 12. Growth hormone induced activation and regulation of JAK2 and STAT proteins.- 13. G protein-coupled-receptor mediated STAT activation.- 14. Regulation of STATs by posttranslational modifications.- 15. Interactions of STATs with SRC family kinases.- 16. The role of phosphatases and reactive oxygen species in regulation of the JAK/STAT pathway.- 17. Raft-STAT signaling and transcytoplasmic trafficking.- 18. Nuclear trafficking of STAT proteins.- 19. Interaction of STAT signals with other signaling pathways.- 20. Forward genetics in mammalian cells.- 21. X-ray crystal structure of STAT proteins and structure-activity relationships.- 22. STAT transcriptional activation mechanisms: communication with the basal transcriptional machinery.- 23. STAT-dependent gene expression without tyrosine phosphorylation.- Section III Biological Impact of Stat Activation.- 24. JAK/STAT signaling: a tale of jeeps and trains.- 25. Viruses and STAT proteins: co-evolution with the JAK-STAT pathway.- 26. STATs in immune responses to viral infections.- 27. IFN, receptor-STAT1 signaling and cancer immunoediting.- 28. STAT activation in TH1/TH2 differentiation.- 29. Mechanisms and biological consequences of STAT signaling by cytokines that share the common cytokine receptor ? chain, ?C 435.- 30. STAT activation in the acute phase response.- 31. STAT3 function in vivo.- 32. Tissue-specific function of STAT3.- 33. Role of STATs in the biological functions of growth hormone.- 34. STAT/SOCS family members in inflammation and diseases.- 35. Signal Transducers and Activators of Transcription in cytokine signaling.- 36. STAT signaling by erythropoietin.- 37. STATs in cell mobility and polarity during morphogenetic movement.- 38. Negative regulators of STAT function in Drosophila.- 39. Jak3 and the pathogenesis of severe combined immunodeficiency.- 40. Constitutively active STATs and cellular transformation.- 41. STAT proteins as molecular targets for cancer therapy.- 42. STATs in the central nervous system.- 43. STATs in the cardiovascular system.- 44. JAKs and STATs as biomarkers of disease.- 45. Drug discovery approaches targeting the JAK/STAT pathway.- Author Index.
1. Introduction: a brief history of the STATs and a glance at the future.- Section I Stat Proteins and Their Regulators.- 2. The STAT protein family.- 3. The Janus kinase protein family.- 4. Structural bases of receptor-JAK-STAT interactions.- 5. SOCS proteins: negative regulators of the JAK/STAT pathway.- 6. The PIAS protein family and TC-PTP.- 7. Prime time for the Drosophila JAK/STAT pathway.- 8. The STAT proteins of Dictyostelium.- 9. JAK/STATs in zebrafish: conservation of JAK/STAT signaling in vertebrates.- Section II Mechanisms of Activation of and Transcriptional Regulation by Stat Proteins.- 10. IFNs and STATs, an incestuous relationship.- 11. Mechanisms and biological roles of STAT activation by the IL-6 family of cytokines.- 12. Growth hormone induced activation and regulation of JAK2 and STAT proteins.- 13. G protein-coupled-receptor mediated STAT activation.- 14. Regulation of STATs by posttranslational modifications.- 15. Interactions of STATs with SRC family kinases.- 16. The role of phosphatases and reactive oxygen species in regulation of the JAK/STAT pathway.- 17. Raft-STAT signaling and transcytoplasmic trafficking.- 18. Nuclear trafficking of STAT proteins.- 19. Interaction of STAT signals with other signaling pathways.- 20. Forward genetics in mammalian cells.- 21. X-ray crystal structure of STAT proteins and structure-activity relationships.- 22. STAT transcriptional activation mechanisms: communication with the basal transcriptional machinery.- 23. STAT-dependent gene expression without tyrosine phosphorylation.- Section III Biological Impact of Stat Activation.- 24. JAK/STAT signaling: a tale of jeeps and trains.- 25. Viruses and STAT proteins: co-evolution with the JAK-STAT pathway.- 26. STATs in immune responses to viral infections.- 27. IFN, receptor-STAT1 signaling and cancer immunoediting.- 28. STAT activation in TH1/TH2 differentiation.- 29. Mechanisms and biological consequences of STAT signaling by cytokines that share the common cytokine receptor ? chain, ?C 435.- 30. STAT activation in the acute phase response.- 31. STAT3 function in vivo.- 32. Tissue-specific function of STAT3.- 33. Role of STATs in the biological functions of growth hormone.- 34. STAT/SOCS family members in inflammation and diseases.- 35. Signal Transducers and Activators of Transcription in cytokine signaling.- 36. STAT signaling by erythropoietin.- 37. STATs in cell mobility and polarity during morphogenetic movement.- 38. Negative regulators of STAT function in Drosophila.- 39. Jak3 and the pathogenesis of severe combined immunodeficiency.- 40. Constitutively active STATs and cellular transformation.- 41. STAT proteins as molecular targets for cancer therapy.- 42. STATs in the central nervous system.- 43. STATs in the cardiovascular system.- 44. JAKs and STATs as biomarkers of disease.- 45. Drug discovery approaches targeting the JAK/STAT pathway.- Author Index.
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