A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2 domain and nuclear signaling motifs.
Nck is a small protein composed of Src homology regions (SH) 2 and 3, paralleling the adaptors c-Crk and Grb2/Ash, but its function remains enigmatic. To clarify Nck signaling, a human brain cDNA library was searched for targets of the SH3 moiety of Nck. A novel molecule detected therefrom (referred to as Nck-, Ash- and phospholipase Cgamma-binding protein 4) contained proline-rich sequences and, through the function of one of them, interacted with the middle SH3 domain of Nck. A NAP4 fusion peptide exhibited an affinity for Nck, Ash and phospholipase Cgamma in whole cell lysates. NAP4 also had an SH2 domain, which could bind to activated EGF receptor. These intermolecular interactions imply the intricacy of Nck-mediated signaling around the receptor protein-tyrosine kinases. In addition, NAP4 bore a putative nuclear localization signal and a Q-run/P-run composite, both characteristic of nuclear proteins, and might therefore relate to the presence of Nck in the cellular nucleus.
Matuoka
K
K
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Miki
H
H
Takahashi
K
K
Takenawa
T
T
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D005333:Fetus; D005347:Fibroblasts; D051380:GRB2 Adaptor Protein; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D051966:Phospholipase C gamma; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D007527:Isoenzymes; D008024:Ligands; C078332:Nck protein; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011506:Proteins; C108775:SOCS7 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D010738:Type C Phospholipases; D051966:Phospholipase C gamma