Several signaling systems downstream of G-CSFR have been identified that are defective or hyperactivated in myeloid cells of patients with congenital neutropenia: severely reduced expression of myeloid-specific transcription factors LEF-1 and C/EBPα, severely reduced expression and functions of HCLS1 protein, severely reduced expression of neutrophil elastase protein, dramatic compensatory up-regulation of the NAMPT/NAD + /SIRT pathway leading to continuous activation of emergency granulopoiesis via the transcription factor C/EBPβ, and hyperactivation of STAT5 protein by tyrosine phosphorylation.
Key points
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Severely reduced expression of myeloid-specific transcription factors, lymphoid enhancer binding factor 1 (LEF-1) and C/EBPα.
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Severely reduced expression and functions of HCLS1 protein.
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Severely reduced expression of neutrophil elastase (NE) protein.
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Dramatic compensatory up-regulation of the nicotinamide phosphoribosyltransferase (NAMPT)/NAD + /SIRT pathway, leading to continuous activation of emergency granulopoiesis via the transcription factor C/EBPβ.
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Hyperactivation of STAT5 protein by tyrosine phosphorylation.
Related posts:
Genetics and Pathophysiology of Severe Congenital Neutropenia Syndromes Unrelated to Neutrophil Elastase
Defective G-CSFR Signaling Pathways in Congenital Neutropenia
Granulocyte Colony-Stimulating Factor Receptor Signaling
Chronic Granulomatous Disease
Epidemiology of Congenital Neutropenia
Animal Models of Human Granulocyte Diseases
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