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Untersuchte Arbeit:
Seite: 11, Zeilen: 1 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
This includes activation of tyrosine kinases such

as focal adhesion kinase, pp60src, and c-Abl, MAP kinases, jun Kinase (JNK), and protein kinase C (PKC) [22]. Mediators of cell growth and differentiation such as c-src, phosphoinositides, protein kinase C, and growth factor-mediated signaling pathways are also modulated by cytokines. Cytokines including interleukin-3 and GM-CSF induce cell proliferation, while other cytokines including flt-3 ligand and kit ligand protect cells from apoptosis and sensitize them to the effects of growth promoting cytokines [23-25]. Cytokines may also facilitate the interactions between stem cells and elements in the microenvironment including extracellular matrix (ECM) components [26]. Regulators of HSC including transforming growth factor-beta (TGF-􀈕) and tumor necrosis factor-alpha (TNF-􀄮) modulate cell cycle activity and engraftment [27]. Some cytokines including Wnt and the notch ligand family may also have important effects on stem cell biology [28, 29]. Some cytokines, including TNF-􀄮, may be either inhibitory or activating depending on their concentration and other ongoing physiologic processes [30]. Several known cytokines, such as kit ligand, exist in either a soluble or membrane-bound form and have different activities depending on whether they are bound or soluble and on the environmental context in which they are acting [25]. Hematopoietic regulatory cytokines are produced through both autocrine and paracrine mechanisms and in many cases are produced by non-hematopoietic cells including bone marrow stroma and endothelium.

Chemokines are another class of compounds that are important regulators of hematopoiesis [31-33]. These molecules regulate blood cell trafficking and homing to sites of need and may also be negative and positive growth regulators [34]. Chemokines are composed of a large family of proteins that mediate a variety of processes including inflammation, leukocyte migration and development, angiogenesis, and tumor cell growth and metastasis. Chemokines bind to one or more of a large family of structurally related guanine protein-coupled transmembrane receptors. In hematopoiesis, chemokines inhibit progenitor growth, regulate migration of hematopoietic progenitors. For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential for trafficking of hematopoietic cells in the developing embryo, mediating [homing of HSC and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes [31].]

This includes activation of a tyrosine kinases such as focal adhesion kinase, pp60src, and c-Abl, MAP kinases, jun Kinase (JNK), and protein kinase C (PKC).[38] Mediators of cell growth and differentiation such as c-src, phosphoinositides, protein kinase C, and growth factor-mediated signaling pathways are also modulated by cytokines. Cytokines including interleukin-3 and GM-CSF induce cell proliferation, while other cytokines including flt-3 ligand and kit ligand protect cells from apoptosis and sensitize them to the effects of growth promoting cytokines.[39-41] Cytokines may also facilitate the interactions between stem cells and elements in the microenvironment including extracellular matrix (ECM) components.[42] Regulators of HSCs including transforming growth factor-beta (TGF- ) and tumor necrosis factor-alpha (TNF- ) modulate cell cycle activity and engraftment.[43] Newly discovered cytokines including Wnt and the notch ligand family may also have important effects on stem cell biology.[44,45] Some cytokines, including TNF- , may be either inhibitory or activating depending on their concentration and other ongoing physiologic processes.[46] Several known cytokines, such as kit ligand, exist in either a soluble or membrane-bound form and have different activities depending on whether they are bound or soluble and on the environmental context in which they are acting.[41] Hematopoietic regulatory cytokines are produced through both autocrine and paracrine mechanisms and in many cases are produced by nonhematopoietic cells including bone marrow stroma and endothelium.

Chemokines are another class of compounds that are important regulators of hematopoiesis.[47-49] These molecules regulate blood cell trafficking and homing to sites of need and may also be negative and positive growth regulators.[50] Chemokines are composed of a large family of proteins that mediate a variety of processes including inflammation, leukocyte migration and development, angiogenesis, and tumor cell growth and metastasis. Chemokines bind to one or more of a large family of structurally related guanine protein-coupled transmembrane receptors. In hematopoiesis, chemokines can inhibit progenitor growth, regulate migration of hematopoietic progenitors, and mediate T-cell development in the thymus. For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential for trafficking of hematopoietic cells in the developing embryo, mediating homing of HSCs and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes.[47]

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