Premium
Integrative nuclear FGFR1 signaling (INFS) as a part of a universal “feed‐forward‐and‐gate” signaling module that controls cell growth and differentiation
Author(s) -
Stachowiak Michal K.,
Fang Xiaohong,
Myers Jason M.,
Dunham Star M.,
Berezney Ronald,
Maher Pamela A.,
Stachowiak Ewa K.
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10606
Subject(s) - microbiology and biotechnology , biology , fibroblast growth factor receptor 1 , transcription factor , signal transduction , nuclear export signal , nuclear localization sequence , cell nucleus , nuclear transport , fibroblast growth factor , nucleus , genetics , receptor , gene
A novel signaling mechanism is described through which extracellular signals and intracellular signaling pathways regulate proliferation, growth, differentiation, and other functions of cells in the nervous system. Upon cell stimulation, fibroblast growth factor receptor‐1 (FGFR1), a typically plasma membrane‐associated protein, is released from ER membranes into the cytosol and translocates to the cell nucleus by an importin‐β‐mediated transport pathway along with its ligand, FGF‐2. The nuclear accumulation of FGFR1 is activated by changes in cell contacts and by stimulation of cells with growth factors, neurotransmitters and hormones as well as by a variety of different second messengers and thus was named integrative nuclear FGFR1 signaling (INFS). In the nucleus, FGFR1 localizes specifically within nuclear matrix‐attached speckle‐domains, which are known to be sites for RNA Pol II‐mediated transcription and co‐transcriptional pre‐mRNA processing. In these domains, nuclear FGFR1 colocalizes with RNA transcription sites, splicing factors, modified histones, phosphorylated RNA Pol II, and signaling kinases. Within the nucleus, FGFR1 serves as a general transcriptional regulator, as indicated by its association with the majority of active nuclear centers of RNA synthesis and processing, by the ability of nuclear FGFR1 to activate structurally distinct genes located on different chromosomes and by its stimulation of multi‐gene programs for cell growth and differentiation. We propose that FGFR1 is part of a universal “feed‐forward‐and‐gate” signaling module in which classical signaling cascades initiated by specific membrane receptors transmit signals to sequence specific transcription factors (ssTFs), while INFS elicited by the same stimuli feeds the signal forward to the common coactivator, CREB‐binding protein (CBP). Activation of CBP by INFS, along with the activation of ssTFs by classical signaling cascades brings about coordinated responses from structurally different genes located at different genomic loci. © 2003 Wiley‐Liss, Inc.