RGD Reference Report - Changes in the balance between caldesmon regulated by p21-activated kinases and the Arp2/3 complex govern podosome formation. - Rat Genome Database

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Changes in the balance between caldesmon regulated by p21-activated kinases and the Arp2/3 complex govern podosome formation.

Authors: Morita, T  Mayanagi, T  Yoshio, T  Sobue, K 
Citation: Morita T, etal., J Biol Chem. 2007 Mar 16;282(11):8454-63. Epub 2007 Jan 15.
RGD ID: 2306207
Pubmed: PMID:17224451   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M609983200   (Journal Full-text)

Podosomes are dynamic cell adhesion structures that degrade the extracellular matrix, permitting extracellular matrix remodeling. Accumulating evidence suggests that actin and its associated proteins play a crucial role in podosome dynamics. Caldesmon is localized to the podosomes, and its expression is down-regulated in transformed and cancer cells. Here we studied the regulatory mode of caldesmon in podosome formation in Rous sarcoma virus-transformed fibroblasts. Exogenous expression analyses revealed that caldesmon represses podosome formation triggered by the N-WASP-Arp2/3 pathway. Conversely, depletion of caldesmon by RNA interference induces numerous small-sized podosomes with high dynamics. Caldesmon competes with the Arp2/3 complex for actin binding and thereby inhibits podosome formation. p21-activated kinases (PAK)1 and 2 are also repressors of podosome formation via phosphorylation of caldesmon. Consequently, phosphorylation of caldesmon by PAK1/2 enhances this regulatory mode of caldesmon. Taken together, we conclude that in Rous sarcoma virus-transformed cells, changes in the balance between PAK1/2-regulated caldesmon and the Arp2/3 complex govern the formation of podosomes.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Arpc2Ratpositive regulation of podosome assembly  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Actr3Ratpodosome  IDA  RGD 
Arpc2Ratpodosome core  IDA  RGD 
Arpc2Ratpodosome ring  IDA  RGD 
Arpc2Ratruffle membrane  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Actr3  (actin related protein 3)
Arpc2  (actin related protein 2/3 complex, subunit 2)


Additional Information