Immunodeficiencies and haematological disorders--direct connections to cellular signalling pathways.
Extracellular signals, such as cytokines and foreign antigens, regulate the development and activation of haematopoietic cells through receptor-mediated transcriptional responses. Investigation of the biochemical events that transduce receptor activation to intracellular signal transduction have revealed a general mechanism for both the antigen receptor and the cytokine receptor nuclear signalling. Receptor stimulation is coupled to down-stream signalling cascades through activation of cytoplasmic tyrosine kinases but both receptor types utilize distinct signalling proteins. Antigen receptors employ protein tyrosine kinases of the Src, Syk, and Tec families which phosphorylate and activate cytoplasmic signalling proteins leading to activation of NF-AT, AP-1 and NF-kappaB transcription factors, while the principal signal transducers for cytokine receptors are the Jak tyrosine kinases and Stat transcription factors. The molecular basis for several immune and haematological disorders has been characterized during the last few years and they have been found to be caused by defects in various signalling proteins. In this review the aetiology of immune and haematological disorders is discussed in the light of the recent developments in signal transduction.
Silvennoinen
O
O
Institute of Medical Technology, University of Tampere, Department of Clinical Microbiology, Tampere University Hospital, Finland. ltolsi@uta.fi
D000941:Antigens / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D003593:Cytoplasm / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000502:physiology; D004792:Enzyme Precursors / Q000502:physiology; D006402:Hematologic Diseases / Q000209:etiology* / Q000503:physiopathology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D053616:Janus Kinase 3; D016328:NF-kappa B / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000072377:Syk Kinase; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D018909:src Homology Domains / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology
D000941:Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases