Phosphorylation of Nck in response to a variety of receptors, phorbol myristate acetate, and cyclic AMP.
The 47-kDa protein coimmunoprecipitated with phospholipase C (PLC)-gamma 1 by anti-PLC-gamma 1 monoclonal antibodies is proved to be Nck, a protein composed almost exclusively of one SH2 and three SH3 domains. Nck and PLC-gamma 1 are recognized by certain anti-PLC-gamma 1 monoclonal antibodies because Nck and PLC-gamma 1 share an epitope that likely is located in their SH3 domains. Nck is widely distributed in rat tissues, with an especially high level of expression in testes. The expression levels of Nck remains unchanged during the development of rat brain, whereas PLC-gamma 1 decreases during the same developmental period. Stimulation of A431 cells with epidermal growth factor elicits the tight association of Nck with the epidermal growth factor receptor and phosphorylation of Nck on both serine and tyrosine residues. The phosphorylation of Nck is also enhanced in response to stimulation of the nerve growth factor receptor in PC12 cells, the T-cell receptor complex in Jurkat cells, the membrane immunoglobulin M in Daudi cells, and the low-affinity immunoglobulin G receptor (Fc gamma RII) in U937 cells. The phosphorylation of Nck was also enhanced following treatment of A431 cells with phorbol 12-myristate 13-acetate or forskolin. These results suggest that Nck is a target for a variety of protein kinases that might modulate the postulated role of Nck as an adaptor for the physical and functional coordination of signalling proteins.
Park
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Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Rhee
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SG
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002846:Chromatography, Affinity; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000502:physiology; D015151:Immunoblotting; D007700:Kinetics; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009928:Organ Specificity; D016716:PC12 Cells; D010766:Phosphorylation; D011233:Precipitin Tests; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013912:Threonine / Q000378:metabolism; D010738:Type C Phospholipases / Q000302:isolation & purification
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; C078332:Nck protein; D015513:Oncogene Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D005576:Colforsin; D013912:Threonine; D012694:Serine; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate