Nuclear targeting by growth factors, cytokines, and their receptors: a role in signaling?

Jans, David A.; Hassan, Ghali

doi:10.1002/(sici)1521-1878(199805)20:5<400::aid-bies7>3.0.co;2-r

Cited by 151 publications

(93 citation statements)

References 81 publications

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“…Inflammatory cytokine receptors, such as, those of interleukin-1 (IL-1), IL-5 and interferon-g (IFN-g) also exist in the nuclear compartment (Curtis et al, 1990;Jans and Hassan, 1998;Larkin et al, 2000). In line with these observations, ligands to most of these receptors were also found in the nucleus (Raper et al, 1987;Curtis et al, 1990;Jans and Hassan, 1998;Schausberger et al, 2003).…”

Section: Nuclear Existence Of Other Rtksmentioning

confidence: 96%

“…Several other RTKs, including TrkA,B/NGFR, FGFR, VEGF receptor 2 (VEGFR-2) and type I TGF-b receptor also undergo nuclear transport (Rakowicz-Szulczynska et al, 1988;Maher, 1996;Zwaagstra et al, 2000;Pillai et al, 2005). Inflammatory cytokine receptors, such as, those of interleukin-1 (IL-1), IL-5 and interferon-g (IFN-g) also exist in the nuclear compartment (Curtis et al, 1990;Jans and Hassan, 1998;Larkin et al, 2000). In line with these observations, ligands to most of these receptors were also found in the nucleus (Raper et al, 1987;Curtis et al, 1990;Jans and Hassan, 1998;Schausberger et al, 2003).…”

Section: Nuclear Existence Of Other Rtksmentioning

confidence: 99%

“…Upon DNA damage and oxidative/heat stress, EGFR enters the cell nucleus and interacts with DNA-PK, leading to DNA repair and radioresistance. (Jans and Hassan, 1998;Larkin et al, 2000), IL-1R (Curtis et al, 1990) also localize in the nucleus as intact receptors. Spliced variants of cell-surface FGFR1 and the intracellular domain of HER-4 have been found to enter the cell nucleus (Stachowiak et al, 1997;Ni et al, 2001Ni et al, , 2003; however, it is yet clear whether TrkA, TrkB (Zhang et al, 2003), type I TGF-b receptor (Zwaagstra et al, 2000) and IL-5R (Jans et al, 1997) undergo nuclear translocalization as full-length receptors.…”

Section: Potential Mechanisms For Nuclear-cytoplasmic Transport Of Cementioning

confidence: 99%

“…Nuclear import of cell-surface receptors has been shown to occur in ligand-dependent and -independent manners. Ligand stimulation activates nuclear translocalization of many cell-surface receptors including EGFR, FGFR, IFN-gR, IL-1R, type I TGF-b receptor and IL-5R (Curtis et al, 1990;Jans and Hassan, 1998;Larkin et al, 2000;Zwaagstra et al, 2000;Lin et al, 2001). In the case of HER-2 which lacks the domain/ability for ligand-binding, its kinase activity is required for nuclear entry (Wang et al, 2004).…”

Section: Potential Mechanisms For Nuclear-cytoplasmic Transport Of Cementioning

confidence: 99%

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Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

2006

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Emerging evidences suggest the existence of a new mode of epidermal growth factor receptor (EGFR) signalling pathway in which activated EGFR undergoes nuclear translocalization and subsequently regulates gene expression and potentially mediates other cellular processes. This signalling route is distinct from the better-characterized, traditional EGFR pathway that involves transduction of mitogenic signals through activation of multiple signalling cascades. Transcriptional activity of nuclear EGFR appears to depend on its C-terminal transactivation domain and its physical and functional interaction with other transcription factors that contain DNAbinding activity. Likely via its ability to upregulate gene expression, nuclear EGFR pathway is associated with major characteristics of more aggressive tumours: increased proliferative potential, nitric oxide synthesis, and accelerated G1/S cell cycle progression. A role of nuclear EGFR in prognostic prediction is further suggested in patients with breast carcinomas and oropharyngeal squamous cell carcinomas. It is noted that significant advances were made towards the knowledge of the nuclear EGFR pathway; however, many aspects of this new pathway remain unresolved and will be discussed in this review. As a number of other receptor tyrosine kinases (RTKs) and cytokine receptors also undergo similar nuclear translocalization, a better understanding of the physiological and malignant nature of the nuclear EGFR pathway will likely shed light into the biology of cancer with nuclear RTKs.

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Section: Nuclear Existence Of Other Rtksmentioning

confidence: 96%

Section: Nuclear Existence Of Other Rtksmentioning

confidence: 99%

Section: Potential Mechanisms For Nuclear-cytoplasmic Transport Of Cementioning

confidence: 99%

Section: Potential Mechanisms For Nuclear-cytoplasmic Transport Of Cementioning

confidence: 99%

See 2 more Smart Citations

Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

2006

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“…In addition to messengers released from intracellular membrane stores, there is an increasing body of evidence that endocytosis and endosomes bearing internalized plasma membrane components play an active signaling role in addition to a mechanism of down regulating surface signals [51]. A number of extracellular signal polypeptides and their receptors internalized by endocytosis appear in the nucleus, although their precise function there remains obscure [52]. This includes members of the FGF family and the FGFR complex [53,54] with which LRPPRC appears in cell extracts [1,2, unpublished results].…”

Section: Conclusion and Predictionsmentioning

confidence: 99%

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

2002

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LRPPRC (originally called LRP130) is an intracellular 130-kDa leucine-rich protein that copurifies with the FGF receptor from liver cell extracts and has been detected in diverse multiprotein complexes from the cell membrane, cytoskeleton and nucleus. Here we report results of a sequence homology analysis of LRPPRC and its SEC1 domain interactive partners. Twenty-three copies of tandem repeats that are similar to PPR, TPR and HEAT repeats characterize the LRPPRC sequence. The N-terminus exhibits multiple copies of leucine-rich nuclear transport signals followed by ENTH, DUF28 and SEC1 homology domains. We used the SEC1 domain to trap interactive partners expressed from a human liver cDNA library. Interactive C19ORF5 (XP_038600) exhibited a strong homology to microtubule-associated proteins (MAP) and a potential arginine-rich mRNA binding motif. UXT (XP_033860) exhibited α-helical properties homologous to the actin-associated spectrin repeat and L/I heptad repeats in mobile transcription factors. C6ORF34 (XP_004305) was homologous to the non-DNA binding C-terminus of the E. coli Rob transcription factor. CECR2 (AAK15343) exhibited a transcription factor AT-hook motif next to two bromodomains and a homology to guanylate-binding protein 1. Taken together these features suggest a regulatory role of LRPPRC and its SEC1 domain-interactive partners in integration of cytoskeletal networks with vesicular trafficking, nucleocytosolic shuttling, chromosome remodeling and transcription.

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The mitogenic activity of fibroblast growth factor-1 correlates with its internalization and limited proteolytic processing

Grieb

Burgess

2000

J. Cell. Physiol.

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The fibroblast growth factor-1 (FGF-1) mitogenic signal transduction pathway is not well characterized, and evidence indicates that FGF-1 binding to and activation of cell-surface receptors is not solely sufficient for a full mitogenic response. Although initiation of the phosphorylation signaling cascades are likely important in FGF-1-induced mitogenic signaling, there appear to be additional signaling requirements. In this study, we demonstrate that FGF-1 internalization and subsequent processing correlates with the mitogenic potential of the growth factor on NIH 3T3 cells. Using site-directed mutants of FGF-1 and inhibitors of the endocytic and degradative pathways, we provide evidence for growth factor internalization and exposure to an acidic environment as necessary components of FGF-1-induced mitogenesis. In addition, a protease-sensitive event(s) appears critical for a complete mitogenic response to FGF-1, whereas, this protease sensitivity was not detected under the same conditions for serum-stimulated mitogenesis. Therefore, proteolytic modification of internalized FGF-1 may result in the activation of additional, intracellular signaling events.

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Nuclear targeting by growth factors, cytokines, and their receptors: a role in signaling?

Cited by 151 publications

References 81 publications

Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

The mitogenic activity of fibroblast growth factor-1 correlates with its internalization and limited proteolytic processing

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