Kank attenuates actin remodeling by preventing interaction between IRSp53 and Rac1.
In this study, insulin receptor substrate (IRS) p53 is identified as a binding partner for Kank, a kidney ankyrin repeat-containing protein that functions to suppress cell proliferation and regulate the actin cytoskeleton. Kank specifically inhibits the binding of IRSp53 with active Rac1 (Rac1(G12V)) but not Cdc42 (cdc42(G12V)) and thus inhibits the IRSp53-dependent development of lamellipodia without affecting the formation of filopodia. Knockdown (KD) of Kank by RNA interference results in increased lamellipodial development, whereas KD of both Kank and IRSp53 has little effect. Moreover, insulin-induced membrane ruffling is inhibited by overexpression of Kank. Kank also suppresses integrin-dependent cell spreading and IRSp53-induced neurite outgrowth. Our results demonstrate that Kank negatively regulates the formation of lamellipodia by inhibiting the interaction between Rac1 and IRSp53.
Roy
Badal Chandra
BC
Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
Kakinuma
Naoto
N
Kiyama
Ryoiti
R
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C119539:BAIAP2 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C538755:Kank1 protein, mouse; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D020830:rac1 GTP-Binding Protein