Document Detail


APC and Smad7 link TGFβ type I receptors to the microtubule system to promote cell migration.
MedLine Citation:
PMID:  22496417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell migration occurs by activation of complex regulatory pathways that are spatially and temporally integrated in response to extracellular cues. Binding of adenomatous polyposis coli (APC) to the microtubule plus ends in polarized cells is regulated by glycogen synthase kinase 3β (GSK-3β). This event is crucial for establishment of cell polarity during directional migration. However, the role of APC for cellular extension in response to extracellular signals is less clear. Smad7 is a direct target gene for transforming growth factor-β (TGFβ) and is known to inhibit various TGFβ-induced responses. Here we report a new function for Smad7. We show that Smad7 and p38 mitogen-activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGFβ stimulation. In addition, Smad7 forms a complex with APC and acts as an adaptor protein for p38 and GSK-3β kinases to facilitate local TGFβ/p38-dependent inactivation of GSK-3β, accumulation of β-catenin, and recruitment of APC to the microtubule plus end in the leading edge of migrating prostate cancer cells. Moreover, the Smad7-APC complex links the TGFβ type I receptor to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFβ.
Authors:
Maria Ekman; Yabing Mu; So Young Lee; Sofia Edlund; Takaharu Kozakai; Noopur Thakur; Hoanh Tran; Jiang Qian; Joanna Groeden; Carl-Henrik Heldin; Maréne Landström
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-11
Journal Detail:
Title:  Molecular biology of the cell     Volume:  23     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-31     Completed Date:  2012-09-24     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2109-21     Citation Subset:  IM    
Affiliation:
Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / drug effects,  metabolism
Adenomatous Polyposis Coli Protein / metabolism*
Animals
Cell Line, Tumor
Cell Movement* / drug effects
Cell Polarity / drug effects
Enzyme Activation / drug effects
Glycogen Synthase Kinase 3 / metabolism
Humans
Male
Mice
Microtubules / drug effects,  metabolism*
Models, Biological
Prostatic Neoplasms / enzymology,  pathology
Protein Binding / drug effects
Protein-Serine-Threonine Kinases / metabolism*
Pseudopodia / drug effects,  metabolism
Receptors, Transforming Growth Factor beta / metabolism*
Smad7 Protein / metabolism*
Transforming Growth Factor beta / pharmacology
beta Catenin / metabolism
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Adenomatous Polyposis Coli Protein; 0/Receptors, Transforming Growth Factor beta; 0/SMAD7 protein, human; 0/Smad7 Protein; 0/Transforming Growth Factor beta; 0/beta Catenin; EC 2.7.1.11/TGF-beta type I receptor; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.11.26/Glycogen Synthase Kinase 3
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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