Mouse alpha1-syntrophin binding to Grb2: further evidence of a role for syntrophin in cell signaling.
Syntrophins have been proposed to serve as adapter proteins. Syntrophins are found in the dystrophin glycoprotein complex (DGC); defects in the constituents of this complex are linked to various muscular dystrophies. Blot overlay experiments demonstrate that alpha-dystroglycan, beta-dystroglycan, and syntrophins all bind Grb2, the growth factor receptor bound adapter protein. Mouse alpha1-syntrophin sequences were produced as chimeric fusion proteins in bacteria and found to also bind Grb2 in a Ca2+-independent manner. This binding was localized to the proline rich sequences adjacent to and overlapping with the N-terminal pleckstrin homology domain (PH1). Grb2 bound syntrophin with an apparent KD of 563 +/- 15 nM. Grb2-C-SH3 domain bound syntrophin with slightly higher affinity than Grb2-N-SH3 domain. Crk-L, an SH2/SH3 protein of similar domain structure but different specificity, does not bind these syntrophin sequences.
Oak
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Department of Biochemistry, 858 Madison Avenue, University of Tennessee, Memphis, Tennessee 38163, USA.
Russo
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K
Petrucci
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TC
Jarrett
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HW
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D049030:Dystroglycans; D051380:GRB2 Adaptor Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C039077:platelet protein P47; C091825:syntrophin alpha1; D049030:Dystroglycans