From Src Homology domains to other signaling modules: proposal of the `protein recognition code'

Sudol, Marius

doi:10.1038/sj.onc.1202182

Cited by 225 publications

(168 citation statements)

References 37 publications

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“…The primary function of RTK tyrosine phosphorylation is to generate binding sites for cytoplasmic or plasma membrane associated proteins involved in transducing proliferative or di erentiating signals to the nucleus. These`signaling proteins' each contain modular Src homology 2 (SH2) (Sadowski et al, 1986) or protein tyrosine binding/ interacting (PTB/PID) (van der Geer et al, 1995) domains and directly interact with phosphotyrosyl proteins in a sequence speci®c manner (reviewed in Pawson and Scott, 1997;Sudol 1998). Such signaling proteins can be loosely grouped into two classes: enzymes and non-enzymatic`adapter' proteins.…”

Section: Erbb-2 Plays a Causal Role In Mammary Tumorigenesismentioning

confidence: 99%

Signal transduction in mammary tumorigenesis: a transgenic perspective

Dankort

Muller

2000

Oncogene

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Section: Erbb-2 Plays a Causal Role In Mammary Tumorigenesismentioning

confidence: 99%

Signal transduction in mammary tumorigenesis: a transgenic perspective

Dankort

Muller

2000

Oncogene

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“…This concept emerged from the discovery that most protein components of these pathways contain discrete and modular protein-protein interaction domains (Sudol, 1998;Pawson, 2004). These domains have so far been characterized mainly for soluble cytoplasmic proteins.…”

Section: Introductionmentioning

confidence: 99%

Transmembrane Domain Interactions Control Biological Functions of Neuropilin-1

Roth

Nasarre

Dirrig‐Grosch

et al. 2008

MBoC

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Neuropilin-1 (NRP1) is a transmembrane receptor playing a pivotal role in the control of semaphorins and VEGF signaling pathways. The exact mechanism controlling semaphorin receptor complex formation is unknown. A structural analysis and modeling of NRP1 revealed a putative dimerization GxxxG motif potentially important for NRP1 dimerization and oligomerization. Our data show that this motif mediates the dimerization of the transmembrane domain of NRP1 as demonstrated by a dimerization assay (ToxLuc assay) performed in natural membrane and FRET analysis. A synthetic peptide derived from the transmembrane segment of NRP1 abolished the inhibitory effect of Sema3A. This effect depends on the capacity of the peptide to interfere with NRP1 dimerization and the formation of oligomeric complexes. Mutation of the GxxxG dimerization motif in the transmembrane domain of NRP1 confirmed its biological importance for Sema3A signaling. Overall, our results shed light on an essential step required for semaphorin signaling and provide novel evidence for the crucial role of transmembrane domain of bitopic protein containing GxxxG motif in the formation of receptor complexes that are a prerequisite for cell signaling.

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“…One possibility is that RSK1 is a dual kinase with independent serine/threonine and tyrosine kinase activities. It is also possible that the phosphorylated tyrosine residues in RSK1 might provide docking sites for phosphotyrosine-binding proteins, such as SH2-or PTB-containing proteins (Sudol, 1998;Margolis et al, 1999) that control distinct KGF-mediated functions.…”

Section: Discussionmentioning

confidence: 99%

“…These data suggested that RSK family proteins have the potential to associate with the KGFR. Because RSK proteins do not contain SH2 or phosphotyrosine-binding domain (PTB) domains, the typical structural motifs that mediate association with receptor tyrosine kinases (RTKs; Sudol, 1998;Margolis et al, 1999), it is possible that the association between the KGFR and RSK involves an adaptor protein or represents an unconventional interaction with a RTK. Indeed, some RTK-interacting proteins have been identified that do not interact via the conventional phosphotyrosine-SH2/PTB-type interactions.…”

mentioning

confidence: 99%

Ribosomal S6 Kinase as a Mediator of Keratinocyte Growth Factor-induced Activation of Akt in Epithelial Cells

Pan

Devaux

Ray

2004

MBoC

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The keratinocyte growth factor receptor (KGFR) is a member of the fibroblast growth factor receptor (FGFR) superfamily. The proximal signaling molecules of FGFRs are much less characterized compared with other growth factor receptors. Using the yeast two-hybrid assay, we have identified ribosomal S6 kinase (RSK) to be a protein that associates with the cytoplasmic domain of the KGFR. The RSK family of kinases controls multiple cellular processes, and our studies for the first time show association between the KGFR and RSK. Using a lung-specific inducible transgenic system we have recently demonstrated protective effects of KGF on the lung epithelium and have demonstrated KGF-induced activation of the prosurvival Akt pathway both in vivo and in vitro. Here we show that a kinase inactive RSK mutant blocks KGF-induced Akt activation and KGF-mediated inhibition of caspase 3 activation in epithelial cells subjected to oxidative stress. It was recently shown that RSK2 recruits PDK1, the kinase responsible for both Akt and RSK activation. When viewed collectively, it appears that the association between the KGFR and RSK plays an important role in KGF-induced Akt activation and consequently in the protective effects of KGF on epithelial cells. INTRODUCTIONThe keratinocyte growth factor receptor (KGFR) is a member of the FGFR (fibroblast growth factor receptor) family. The KGFR is expressed only in epithelial cells and it plays critical roles in the proliferation, migration, and morphogenesis of epithelial cells (Ulich et al., 1994;Wilson et al., 1994;Post et al., 1996;Buckley et al., 1997). The KGFR also plays important roles in skin wound healing and lung epithelial cell survival during injury (Werner et al., 1994;Panos et al., 1995;Yi et al., 1996;Barazzone et al., 1999;Das and Olsen, 2001;Ray et al., 2003). The KGFR is activated by FGF-1, FGF-3, KGF/FGF-7, and FGF-10, whereas FGFR2 is mainly activated by FGF-2/bFGF (Bottaro et al., 1990;Miki et al., 1991Miki et al., , 1992Orr-Urtreger et al., 1993). In contrast to information on signaling by other growth factor receptors, the proximal signaling molecules of FGFRs are much less characterized.To characterize the KGFR-induced signaling pathways, we screened for proteins interacting with the KGFR cytoplasmic domain using the yeast two-hybrid assay. RSK1 is one of the proteins we identified and this interaction was confirmed in mammalian epithelial cells. The RSK (or p90RSK) family includes three members, RSK1-3, which show 75-80% similarity at the amino acid level (Frodin and Gammeltoft, 1999). RSK family members contain two heterologous kinase domains (Fisher and Blenis, 1996). The Nterminal kinase (NTK) domain belongs to the AGC group of kinases, which includes PKA, PKB/Akt, PKC, and PKG, and is the kinase domain that phosphorylates the substrates of RSKs. The C-terminal kinase (CTK) domain and the linker are involved in the activation of the RSK NTK domain (Frodin and Gammeltoft, 1999). At the carboxyl-terminus, there is an ERK-binding site conserved in all three RSK ...

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From Src Homology domains to other signaling modules: proposal of the `protein recognition code'

Cited by 225 publications

References 37 publications

Signal transduction in mammary tumorigenesis: a transgenic perspective

Signal transduction in mammary tumorigenesis: a transgenic perspective

Transmembrane Domain Interactions Control Biological Functions of Neuropilin-1

Ribosomal S6 Kinase as a Mediator of Keratinocyte Growth Factor-induced Activation of Akt in Epithelial Cells

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