Nuclear signaling by receptor tyrosine kinases: the first robin of spring.
The role of receptor tyrosine kinases (RTKs) in transmembrane signaling is well established. Recently, ligand-dependent translocation of RTKs to the nucleus has been reported, but the functional importance of this process remains unclear. In this issue, Sardi et al. (2006) provide evidence for direct signaling in the nucleus by an intracellular ErbB4 receptor fragment that is released upon receptor activation by ligand. The fragment forms a complex with the adaptor TAB2 and the corepressor N-CoR and transits to the nucleus, where it represses transcription of genes that promote the formation of astrocytes.
Schlessinger
Joseph
J
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. joseph.schlessinger@yale.edu
Lemmon
Mark A
MA
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008024:Ligands; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D010446:Peptide Fragments / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D066247:Receptor, ErbB-4; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D010446:Peptide Fragments; D012097:Repressor Proteins; C410585:TAB2 protein, human; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4