Molecular understanding of hematopoietin/cytokine receptor signaling defects in hematopoietic disorders.
Hematopoietic growth factors (HGFs) act on the hematopoietic cells via binding to specific cell surface receptors. Many HGF receptors have certain common structural features and have therefore been grouped in the superfamily of hematopoietin or cytokine receptors, also referred to as the class I receptor superfamily [1, 2]. Activation of these receptors by their cognate growth factors is mediated through the formation of dimeric or oligomeric complexes of receptor structures. Some HGF receptors are composed of heteromeric complexes, comprising two or three different receptor chains. For instance, this is the case for receptors of interleukins 2, 3, and 5 and granulocyte-macrophage colony-stimulating factor [3]. Other receptor structures, for example, those of granulocyte colony-stimulating factor and erythropoietin, form homodimeric complexes upon growth factor binding [2, 4]. This brief overview begins with an introduction of the major principles of HGF receptor signaling: this is followed by a discussion of the consequences of HGF receptor signaling defects for the development of disorders of the hematopoietic system and the presentation of clinical examples of such diseases.
Soede-Bobok
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Department of Hematology, Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Touw
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D000818:Animals; D006402:Hematologic Diseases / Q000378:metabolism*; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism*; D006801:Humans; D016184:Receptors, Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
D016298:Hematopoietic Cell Growth Factors; D016184:Receptors, Colony-Stimulating Factor; D018121:Receptors, Cytokine; D017978:Receptors, Growth Factor