BAG3 directly associates with guanine nucleotide exchange factor of Rap1, PDZGEF2, and regulates cell adhesion.
BAG3, a member of the Hsc70 binding co-chaperone BAG-family proteins, has critical roles in regulating actin organization, cell adhesion, cell motility and tumor metastasis. The PDZ domain containing guanine nucleotide exchange factor 2 (PDZGEF2) was cloned as a BAG3-interacting protein. PDZGEF2 induces activation of Rap1 and increases integrin-mediated cell adhesion. The PPDY motif at the C-terminus of PDZGEF2 binds to the WW domain of BAG3 in vitro and in vivo. BAG3 deletion mutant lacking the WW domain lose its cell adhesion and motility activity. Gene knockdown of PDZGEF2 leads to the loss of cell adhesion on fibronectin-coated plates while BAG3 overexpression increases cell adhesion in Cos7 cells, but not in PDZGEF2 gene knockdown cells indicating that PDZGEF2 is a critical partner for BAG3 in regulating cell adhesion.
Iwasaki
Masahiro
M
Medical College of Georgia, 1210 Laney Walker Street, Augusta, GA 92023, USA.
Tanaka
Ryoichi
R
Hishiya
Akinori
A
Homma
Sachiko
S
Reed
John C
JC
Takayama
Shinichi
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D019556:COS Cells; D002448:Cell Adhesion; D002465:Cell Movement; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D020662:Guanine Nucleotide Exchange Factors; C485746:RAPGEF6 protein, human
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