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Identifier 000372850
Title Θετική και αρνητική ρύθμιση των μικρών GTRασων RHO και του κυτταροσκελετού ακτίνης από BMP και TGF-B
Alternative Title Positive and negative regulation of small Gtpases Rho and actin cytoskeleton by BMP and TGF-B
Author Κωνσταντινίδης, Γεώργιος
Thesis advisor Στουρνάρας, Χρήστος
Reviewer Καρδάσης, Δημήτρης
Τσατσάνης, Χρήστος
Μουστάκας, Αριστείδης
Γραβάνης, Αχιλλέας
Σουρβίνος, Γιώργος
Παπακωνσταντή, Ευαγγελία
Abstract Actin cytoskeleton dynamics support and coordinate a large number of signaling events that control cell proliferation, differentiation and migration. Cytoskeletal plasticity is based on multi-­‐protein complexes that regulate actin polymerization, stability and assembly with myosin. Growth factors provide essential signals that govern cytoskeletal dynamics. One such growth factor network is the transforming growth factor β (TGF-­‐β) that includes secreted polypeptides such as bone morphogenetic proteins (BMP) and activins. Here, it is demonstrated that BMP-­‐7 signals through Smad1, p38 and p44/42 (Erk1/2) MAPKs and induces actin polymerization and focal adhesion remodeling in starved fibroblasts and various other cell lines as potently as TGF-­‐β. Moreover, BMP-­‐7 induces migration of Swiss3T3 fibroblasts letting at the same time proliferation and apoptosis unaffected. An important regulator of actin remodeling, the kinase ROCK1 mediates changes of actin dynamics by BMP-­‐7, while this growth factor induces rapid activation of RhoA and RhoB GTPases with concomitant inactivation of Cdc42. In parallel, BMP-­‐7 induces RhoB and Smad6 expression providing with a positive and a negative signalling feedback simultaneously. Activation of Rho GTPases and the downstream ROCK1 kinase by BMP-­‐7 correlate well with induction of phosphorylation on Ser19 of the myosin light chain, but not with LIMK1 kinase activation. ROCK inhibitor Y-­‐27632 blocks actin polymerization and reduces migration capacity induced by BMP-­‐7. Furthermore, the same ROCK inhibitor blocks the myosin light chain phosphorylation of Ser19 during BMP-­‐7 signalling. Depletion of endogenous myosin light chain also inhibits the actin remodeling induced by BMP-­‐7. Thus, in a next step, this novel pathway regulates fibroblast migration without affecting cell proliferation. Taking everything into consideration, here it is established not only that BMP signals through Smad and, the so-­‐called, non-­‐Smad pathway of MAPKs, but also through Rho/ROCK pathway which targets myosin light chain during actin remodeling and migration of Swiss3T3 fibroblasts.
Language Greek
Subject Actin
Biochemistry
Bone morphogenetic protein
Cytoskeleton
Myosin light chain
Myosin light chain kinase
Rho coiled- coiledkinase 1
Transforming growth factor β
Ακτίνη
Ελαφριά αλυσίδα μυοσίνης
Κινάση της ελαφριάς αλυσίδας μυοσίνης
Κυτταροσκελετός
Μετασχηματίζων αυξητικός παράγοντας β
Πρωτεϊνη μορφογένεσης οστών
Issue date 2011-12-14
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/9/2/a/metadata-dlib-1331719544-168672-23176.tkl Bookmark and Share
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