Nuclear localization and possible functions of receptor tyrosine kinases.
Recent data have renewed interest in the possible nuclear localization of receptor tyrosine kinases, as well as their ligands. In one case, that of ErbB-4, the receptor is processed by two membrane-localized proteases to produce a soluble cytoplasmic domain fragment that includes the tyrosine kinase domain. This fragment, generated by a metalloprotease-dependent ectodomain cleavage followed by gamma-secretase cleavage within the transmembrane domain, is also found in the nucleus. Three other receptor tyrosine kinases have been detected in the nucleus in the absence of proteolytic processing. In some instances, nuclear localization of receptor tyrosine kinases is growth-factor-dependent and tentative evidence suggests a role in transcription.
Carpenter
Graham
G
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. graham.carpenter@mcmail.vanderbilt.edu
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000648:ultrastructure; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D066247:Receptor, ErbB-4; D014157:Transcription Factors / Q000502:physiology*
D006133:Growth Substances; D010446:Peptide Fragments; D014157:Transcription Factors; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4