Trafficking and signaling pathways of nuclear localizing protein ligands and their receptors.
Interaction of ligands such as epidermal growth factor and interferon-gamma with the extracellular domains of their plasma membrane receptors results in internalization followed by translocation into the nucleus of the ligand and/or receptor. There has been reluctance, however, to ascribe signaling importance to this, the focus instead being on second messenger pathways, including mobilization of kinases and inducible transcription factors (TFs). The latter, however, fails to explain the fact that so many ligands stimulate the same second messenger cascades/TFs, and yet show distinct gene activation profiles. This is particularly apt in the case of the seven STAT TFs that are held to be the mediators of the distinct cellular functions of over 60 ligands. The current review focuses on five representative nuclear localizing ligands for which there is documentation of translocation into the cytosol and nucleus through well-characterized pathways, in addition to a role in gene activation by ligand/receptor in the nucleus.
Johnson
Howard M
HM
Department of Microbiology and Cell Science, University of Florida, FL, USA. johnsonh@ufl.edu
Subramaniam
Prem S
PS
Olsnes
Sjur
S
Jans
David A
DA
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D019281:Dimerization; D004815:Epidermal Growth Factor / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D011388:Prolactin / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017471:Receptors, Interferon / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D000096743:Interferon gamma Receptor
D004815:Epidermal Growth Factor; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2; D013006:Growth Hormone; D007371:Interferon-gamma; D008024:Ligands; D011388:Prolactin; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor