Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton.
Palladin and alpha-actinin are major components of stress fiber dense bodies, cardiomyocyte Z-discs and neuronal synapses. They function as structural molecules and cytoskeletal regulators but also as docking sites to other proteins. Both antisense and transient overexpression experiments have shown that palladin plays an important role in the regulation of actin cytoskeleton. ArgBP2 is a multi-domain scaffolding protein which shares both the tissue distribution and subcellular localization with palladin. ArgBP2 is directly linked to intracellular signaling cascades by its interaction with Abl family kinases, Pyk2 and the ubiquitin ligase Cbl. It has several actin associated binding partners and has been shown to regulate cytoskeletal dynamics. Here, we show by in vivo and in vitro methods that palladin's amino-terminal poly-proline sequences directly interact with the first carboxy-terminal SH3 domain of ArgBP2. We further demonstrate a direct interaction between alpha-actinin and the amino-terminal segment of ArgBP2. Immunoprecipitation and targeting assays suggest that a three-way complex of the proteins occurs in vivo. The interactions provide an explanation to the previously observed Z-disc-specific localization of ArgBP2 and indicate interplay between signaling adaptors and structural proteins of the Z-disc.
Rönty
Mikko
M
Biomedicum Helsinki, Department of Pathology and Neuroscience Program, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. mikko.ronty@helsinki.fi
Taivainen
Anu
A
Moza
Monica
M
Kruh
Gary D
GD
Ehler
Elisabeth
E
Carpen
Olli
O
D000185:Actinin / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D020798:Two-Hybrid System Techniques
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; C485874:LOC103693936; D010750:Phosphoproteins; C490754:Sorbs2 protein, rat; D000185:Actinin