Ossip Groth am 8. März 2010 um 19:25 Uhr

2010-03-08T19:25:13Z

← Nächstältere Version		Version vom 8. März 2010, 19:25 Uhr
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	\| bgcolor="#00dfdf" \| '''Was ist das'''		\| bgcolor="#00dfdf" \| '''Was ist das'''
	\| align="left" width="800"\| Rezeptorkomponente für [[TGF-beta]], hat [[~~Tyrosinkinase~~]]aktivität, aktiviert [[smad2]]/[[smad3]];[[smad7]], hierdurch [[Signaltransduktion]], beeinflußt Gene mit der Folge [[Antiproliferation]], [[Fibrose]], [[Matrix, extrazellulär\|Matrixproduktion]], [[Epithelio Mesenchymale Transition\|Zelldifferenzierung epithelialer Zellen zum mesenchyalen Charakter hin]], [[Immunsuppression]]. Wichtig für [[Blutgefäß, Entwicklung\|Angiogenese]] und [[Morphogenese\|entwicklungsbiologische Vorgänge]] sowie [[Wundheilung]].		\| align="left" width="800"\| Rezeptorkomponente für [[TGF-beta]], hat [[Serin/Threonin-Kinase]]aktivität, aktiviert [[smad2]]/[[smad3]];[[smad7]], hierdurch [[Signaltransduktion]], beeinflußt Gene mit der Folge [[Antiproliferation]], [[Fibrose]], [[Matrix, extrazellulär\|Matrixproduktion]], [[Epithelio Mesenchymale Transition\|Zelldifferenzierung epithelialer Zellen zum mesenchyalen Charakter hin]], [[Immunsuppression]]. Wichtig für [[Blutgefäß, Entwicklung\|Angiogenese]] und [[Morphogenese\|entwicklungsbiologische Vorgänge]] sowie [[Wundheilung]].
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	\| bgcolor="#dfdfdf" \| '''Struktur'''		\| bgcolor="#dfdfdf" \| '''Struktur'''

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2010-03-08T19:16:39Z

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[[Datei:pptpdtjpg1.png|miniatur|Entstehender Artikel]]
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| bgcolor="#dfdfdf" | '''Siehe auch'''
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| bgcolor="#dfdfdf" | '''Freie Übersichtsartikel'''
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| bgcolor="#dfdfdf" | '''Wichtige Übersichtsartikel'''
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| bgcolor="#dfdfdf" | '''Medline Suchterm/ Synonyme'''
| align="left" width="800"| (alk5 OR alk-5 OR activin-like kinase 5) sowie alle Variationen von (TGF beta type I receptor OR transforming growth factor beta type I receptor)
|-
| bgcolor="#00dfdf" | '''Was ist das'''
| align="left" width="800"| Rezeptorkomponente für [[TGF-beta]], hat [[Tyrosinkinase]]aktivität, aktiviert [[smad2]]/[[smad3]];[[smad7]], hierdurch [[Signaltransduktion]], beeinflußt Gene mit der Folge [[Antiproliferation]], [[Fibrose]], [[Matrix, extrazellulär|Matrixproduktion]], [[Epithelio Mesenchymale Transition|Zelldifferenzierung epithelialer Zellen zum mesenchyalen Charakter hin]], [[Immunsuppression]]. Wichtig für [[Blutgefäß, Entwicklung|Angiogenese]] und [[Morphogenese|entwicklungsbiologische Vorgänge]] sowie [[Wundheilung]].
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| bgcolor="#dfdfdf" | '''Struktur'''
| align="left" width="800"| <ref name="PMID19096363">TGFbeta-stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro-migratory TGFbeta switch. EMBO J 28(2):88-98 (2009) PMID 19096363 </ref>
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| bgcolor="#dfdfdf" | '''Physiologie'''
| align="left" width="800"| [[Signaltransduktion]]: <ref name="PMID15769904">Gene expression profiling demonstrates that TGF-beta1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-beta signaling. Physiol Genomics 21(3):396-403 (2005) PMID 15769904 </ref>

Angiogenese: <ref name="PMID19116361">Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline. Am J Pathol 174(2):380-9 (2009) PMID 19116361 </ref><ref name="PMID18456797">Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5. Am J Physiol Lung Cell Mol Physiol 295(1):L123-33 (2008) PMID 18456797 </ref><ref name="PMID16344855">Nonoverlapping expression patterns of ALK1 and ALK5 reveal distinct roles of each receptor in vascular development. Lab Invest 86(2):116-29 (2006) PMID 16344855 </ref><ref name="PMID17071858">TGFbeta1 induces vasculogenesis and inhibits angiogenic sprouting in an embryonic stem cell differentiation model: respective contribution of ALK1 and ALK5. Stem Cells 24(11):2420-7 (2006) PMID 17071858 </ref><ref name="PMID19398875">TGF-beta inhibits vascular sprouting through TGF-beta type I receptor in the mouse embryonic aorta. Tohoku J Exp Med 218(1):63-71 (2009) PMID 19398875 </ref>

[[Fibrose]]/[[Myofibroblast]]/[[Epithelio Mesenchymale Transition|Epithelio-mesenchymale Transdifferenzierung]]: <ref name="PMID16314481">Matrix contraction by dermal fibroblasts requires transforming growth factor-beta/activin-linked kinase 5, heparan sulfate-containing proteoglycans, and MEK/ERK: insights into pathological scarring in chronic fibrotic disease. Am J Pathol 167(6):1699-711 (2005) PMID 16314481 </ref><ref name="PMID9466575">Enhanced expression of transforming growth factor-beta type I and type II receptors in wound granulation tissue and hypertrophic scar. Am J Pathol 152(2):485-93 (1998) PMID 9466575 </ref><ref name="PMID16575856">Contribution of activin receptor-like kinase 5 (transforming growth factor beta receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblasts. Arthritis Rheum 54(4):1309-16 (2006) PMID 16575856 </ref><ref name="PMID7806579">TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J Cell Biol 127(6 Pt 2):2021-36 (1994) PMID 7806579 </ref><ref name="PMID10574705">TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J Cell Sci 112 ( Pt 24)():4557-68 (1999) PMID 10574705 </ref>

[[Morphogenese|Entwicklungsbiologie]]: <ref name="PMID18718461">Signaling via the Tgf-beta type I receptor Alk5 in heart development. Dev Biol 322(1):208-18 (2008) PMID 18718461 </ref><ref name="PMID17250821">Endoglin and Alk5 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev Biol 304(1):420-32 (2007) PMID 17250821 </ref><ref name="PMID16806156">Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion. Dev Biol 296(2):298-314 (2006) PMID 16806156 </ref><ref name="PMID16258965">Transforming growth factor-beta induces loss of epithelial character and smooth muscle cell differentiation in epicardial cells. Dev Dyn 235(1):82-93 (2006) PMID 16258965 </ref><ref name="PMID16245329">Transforming growth factor-beta stimulates epithelial-mesenchymal transformation in the proepicardium. Dev Dyn 235(1):50-9 (2006) PMID 16245329 </ref><ref name="PMID18586087">Signaling through Tgf-beta type I receptor Alk5 is required for upper lip fusion. Mech Dev 125(9-10):874-82 (2008) PMID 18586087 </ref>

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| bgcolor="#dfdfdf" | '''Knockout'''
| align="left" width="800"| <ref name="PMID17078885">Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects. BMC Dev Biol 6():51 (2006) PMID 17078885 </ref><ref name="PMID10853822">Functional analysis of the TGFbeta receptor/Smad pathway through gene ablation in mice. Int J Dev Biol 44(3):253-65 (2000) PMID 10853822 </ref>
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| bgcolor="#dfdfdf" | '''Transgen'''
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| bgcolor="#dfdfdf" | '''Mutation'''
| align="left" width="800"| <ref name="PMID18339844">Cancer-associated transforming growth factor beta type II receptor gene mutant causes activation of bone morphogenic protein-Smads and invasive phenotype. Cancer Res 68(6):1656-66 (2008) PMID 18339844 </ref><ref name="PMID12700602">Disease-associated mutations in conserved residues of ALK-1 kinase domain. Eur J Hum Genet 11(4):279-87 (2003) PMID 12700602 </ref>
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| bgcolor="#dfdfdf" | '''Polymorphismus'''
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| bgcolor="#dfdfdf" | '''Genexpression'''
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| bgcolor="#dfdfdf" | '''Inhibitoren'''
| align="left" width="800"| Z.B. [[SD208]], [[SM16]], [[SB431542]], [[SB505124]]: <ref name="PMID15563636">Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Am J Respir Crit Care Med 171(8):889-98 (2005) PMID 15563636 </ref><ref name="PMID17526757">SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion. Antimicrob Agents Chemother 51(8):2905-10 (2007) PMID 17526757 </ref><ref name="PMID18202322">SM16, an orally active TGF-beta type I receptor inhibitor prevents myofibroblast induction and vascular fibrosis in the rat carotid injury model. Arterioscler Thromb Vasc Biol 28(4):665-71 (2008) PMID 18202322 </ref><ref name="PMID15593186">Selective inhibition of activin receptor-like kinase 5 signaling blocks profibrotic transforming growth factor beta responses in skin fibroblasts. Arthritis Rheum 50(12):4008-21 (2004) PMID 15593186 </ref><ref name="PMID18474728">Inhibition of the TGF-beta receptor I kinase promotes hematopoiesis in MDS. Blood 112(8):3434-43 (2008) PMID 18474728 </ref><ref name="PMID15723089">Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol 145(2):166-77 (2005) PMID 15723089 </ref><ref name="PMID17332368">A novel small-molecule inhibitor of transforming growth factor beta type I receptor kinase (SM16) inhibits murine mesothelioma tumor growth in vivo and prevents tumor recurrence after surgical resection. Cancer Res 67(5):2351-9 (2007) PMID 17332368 </ref><ref name="PMID14633705">SB-431542 and Gleevec inhibit transforming growth factor-beta-induced proliferation of human osteosarcoma cells. Cancer Res 63(22):7791-8 (2003) PMID 14633705 </ref><ref name="PMID17505012">Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats. Clin Cancer Res 13(10):3087-99 (2007) PMID 17505012 </ref><ref name="PMID18725536">TGFbeta induces SIK to negatively regulate type I receptor kinase signaling. J Cell Biol 182(4):655-62 (2008) PMID 18725536 </ref><ref name="PMID16741519">Intracellular TGF-beta receptor blockade abrogates Smad-dependent fibroblast activation in vitro and in vivo. J Invest Dermatol 126(8):1733-44 (2006) PMID 16741519 </ref><ref name="PMID15769863">Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther 313(3):943-51 (2005) PMID 15769863 </ref><ref name="PMID14978253">SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. Mol Pharmacol 65(3):744-52 (2004) PMID 14978253 </ref><ref name="PMID12065756">SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 62(1):65-74 (2002) PMID 12065756 </ref><ref name="PMID12065755">Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542. Mol Pharmacol 62(1):58-64 (2002) PMID 12065755 </ref><ref name="PMID19081766">Inhibitory effect of blocking TGF-beta/Smad signal on injury-induced fibrosis of corneal endothelium. Mol Vis 14():2272-81 (2008) PMID 19081766 </ref>
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| bgcolor="#dfdfdf" | '''Agonisten'''
| align="left" width="800"| [[TGF-beta]], [[GDF11]] <ref name="PMID16845371">Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis. EMBO Rep 7(8):831-7 (2006) PMID 16845371 </ref>, [[GDF9]]<ref name="PMID14684852">Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. Mol Endocrinol 18(3):653-65 (2004) PMID 14684852 </ref>
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== Bibliographie ==
<references />

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ALK5 - Versionsgeschichte

Ossip Groth am 8. März 2010 um 19:25 Uhr

Ossip Groth: Die Seite wurde neu angelegt: „Entstehender Artikel {| class="wikitable" | | bgcolor="#dfdfdf" | '''Siehe auch''' | align="left" width="800" | |- | bgcolor="#d…“