Identification of Nore1 as a potential Ras effector.
The small GTP-binding protein Ras is pivotal in transmitting growth and differentiation signals downstream of cell surface receptors. Many observations have indicated that Ras transmits signals from cell surface receptors into multiple pathways via direct interaction with different effectors in mammalian cells. We have identified a novel potential Ras effector or target named Nore1. Nore1 has no significant sequence similarity to known mammalian proteins and lacks an identifiable catalytic domain, but contains sequence motifs that predict DAG_PE binding and SH3 domain binding. We show that Nore1 directly interacts with Ras in vitro in a GTP-dependent manner, and the interaction requires an intact Ras effector domain. Nore1 becomes associated with Ras in situ following activation of epidermal growth factor receptor in COS-7 and in KB cells.
Vavvas
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The Diabetes Unit and Medical Services and the Department of Medicine, Harvard Medical School, Massachusetts General Hospital East, Charlestown, Massachusetts 02129, USA.
Li
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X
Avruch
J
J
Zhang
X F
XF
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D006160:Guanosine Triphosphate / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000737:chemistry* / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018631:ras Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C490411:Nr4a3 protein, mouse; C091333:Nr4a3 protein, rat; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D004815:Epidermal Growth Factor; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D018631:ras Proteins; D013755:Tetradecanoylphorbol Acetate