Abstract：
:The 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosine kinases (RTKs) designated FGFR1, FGFR2, FGFR3 and FGFR4. Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and to induce the pleiotropic responses that lead to the variety of cellular responses induced by this large family of growth factors. A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development. Gain of function mutations in FGFRs were also identified in a variety of human cancers such as myeloproliferative syndromes, lymphomas, prostate and breast cancers as well as other malignant diseases. The binding of FGF and HSPG to the extracellular ligand domain of FGFR induces receptor dimerization, activation and autophosphorylation of multiple tyrosine residues in the cytoplasmic domain of the receptor molecule. A variety of signaling proteins are phosphorylated in response to FGF stimulation including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape. The docking proteins FRS2alpha and FRS2beta are major mediators of the Ras/MAPK and PI-3 kinase/Akt signaling pathways as well as negative feedback mechanisms that fine-tune the signal that is initiated at the cell surface following FGFR stimulation.
journal_name
Cytokine Growth Factor Revjournal_title
Cytokine & growth factor reviewsauthors
Eswarakumar VP,Lax I,Schlessinger Jdoi
10.1016/j.cytogfr.2005.01.001subject
Has Abstractpub_date
2005-04-01 00:00:00pages
139-49issue
2eissn
1359-6101issn
1879-0305pii
S1359-6101(05)00002-Xjournal_volume
16pub_type
杂志文章,评审abstract：:Granulocyte colony-stimulating factor (G-CSF) is a pleiotropic cytokine playing a major role as regulator of hematopoiesis and innate immune responses. There is growing evidence that G-CSF also exerts profound immunoregulatory effects in adaptive immunity. G-CSF mediates anti-inflammatory reactions accompanied by TH2 ...
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