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Transforming growth...
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Edlund, SofiaUppsala universitet,Ludwiginstitutet för cancerforskning
(författare)
Transforming growth factor-beta-induced mobilization of actin cytoskeleton required signaling by small GTPases Cdc42 and RhoA
- Artikel/kapitelEngelska2002
Förlag, utgivningsår, omfång ...
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The American Society for Cell Biology,2002
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-90259
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-90259URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Transforming growth factor-beta (TGF-beta) is a potent regulator of cell growth and differentiation in many cell types. The Smad signaling pathway constitutes a main signal transduction route downstream of TGF-beta receptors. We studied TGF-beta-induced rearrangements of the actin filament system and found that TGF-beta 1 treatment of PC-3U human prostate carcinoma cells resulted in a rapid formation of lamellipodia. Interestingly, this response was shown to be independent of the Smad signaling pathway; instead, it required the activity of the Rho GTPases Cdc42 and RhoA, because ectopic expression of dominant negative mutant Cdc42 and RhoA abrogated the response. Long-term stimulation with TGF-beta 1 resulted in an assembly of stress fibers; this response required both signaling via Cdc42 and RhoA, and Smad proteins. A known downstream effector of Cdc42 is p38(MAPK); treatment of the cells with the p38(MAPK) inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(pyridyl)1H-imidazole (SB203580), as well as ectopic expression of a kinase-inactive p38(MAPK), abrogated the TGF-beta-induced actin reorganization. Moreover, treatment of cells with the inhibitors of the RhoA target-protein Rho-associated coiled-coil kinase (+)-R-trans-4-(aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide (Y-27632) and 1-5(-isoquinolinesulfonyl)homopiperazine (HA-1077), as well as ectopic expression of kinase-inactive Rho coiled-coil kinase-1, abrogated the TGF-beta 1-induced formation of stress fibers. Collectively, these data indicate that TGF-beta-induced membrane ruffles occur via Rho GTPase-dependent pathways, whereas long-term effects require cooperation between Smad and Rho GTPase signaling pathways.
Ämnesord och genrebeteckningar
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Actins/*metabolism
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Amides/pharmacology
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Animals
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Cell Surface Extensions/metabolism
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Cytoskeleton/drug effects/*metabolism
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DNA-Binding Proteins/genetics/metabolism
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Enzyme Inhibitors/pharmacology
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Humans
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Imidazoles/pharmacology
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Intracellular Signaling Peptides and Proteins
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Mitogen-Activated Protein Kinases/antagonists & inhibitors/genetics/metabolism
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Protein-Serine-Threonine Kinases/antagonists & inhibitors/genetics/metabolism
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Pyridines/pharmacology
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Rats
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Recombinant Fusion Proteins/metabolism
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Signal Transduction/*physiology
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Smad4 Protein
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Stress Fibers/metabolism
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Trans-Activators/genetics/metabolism
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Transforming Growth Factor beta/*metabolism
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Tumor Cells; Cultured
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cdc42 GTP-Binding Protein/*metabolism
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p38 Mitogen-Activated Protein Kinases
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rac1 GTP-Binding Protein/metabolism
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rhoA GTP-Binding Protein/*metabolism
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Landström, MaréneUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)mareland
(författare)
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Heldin, Carl-HenrikUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)carlheld
(författare)
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Aspenström, PontusUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)pontaspe
(författare)
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Uppsala universitetLudwiginstitutet för cancerforskning
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Molecular Biology of the Cell: The American Society for Cell Biology13:3, s. 902-9141059-15241939-4586
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