Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth factor

Tang, Joel A.; Feng, Gen‐Sheng; Li, Wei

doi:10.1038/sj.onc.1201351

Cited by 36 publications

(24 citation statements)

References 31 publications

(47 reference statements)

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“…Tyrosine phosphorylated Dok can then interact with rasGAP. Additionally, Dok was also phosphorylated upon stimulation of the EphB2 receptor (Holland et al, 1997) and the EGF receptor (Tang et al, 1997) and in both instances, phosphorylated Dok was associated with Nck. Taken together, this suggests that upon tyrosine phosphorylation, Dok and Dok-R may interact with a similar repertoire of downstream substrates.…”

Section: Discussionmentioning

confidence: 95%

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R

1998

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Tek/Tie2 is an endothelial cell-speci®c receptor tyrosine kinase that has been shown to play a role in vascular development of the mouse. Targeted mutagenesis of both Tek and its agonistic ligand, Angiopoietin-1, result in embryonic lethality, demonstrating that the signal transduction pathway(s) mediated by this receptor are crucial for normal embryonic development. In an attempt to identify downstream signaling partners of the Tek receptor, we have used the yeast two-hybrid system to identify phosphotyrosine-dependent interactions. Using this approach, we have identi®ed a novel docking molecule called Dok-R, which has sequence and structural homology to p62 dok and IRS-3. Mapping of the phosphotyrosine-interaction domain within Dok-R shows that Dok-R interacts with Tek through a PTB domain. Dok-R is coexpressed with Tek in a number of endothelial cell lines. We show that coexpression of Dok-R with activated Tek results in tyrosine phosphorylation of Dok-R and that rasGAP and Nck coimmunoprecipitate with phosphorylated Dok-R. Furthermore, Dok-R is constitutively bound to Crk presumably through the proline rich tail of Dok-R. The cloning of Dok-R represents the ®rst downstream substrate of the activated Tek receptor, and suggests that Tek can signal through a multitude of pathways.

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Section: Discussionmentioning

confidence: 95%

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R

1998

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“…On the other hand, several tyrosine phosphorylation sites are present creating docking sites for Src homology 2 (SH2) domain-containing adapter molecules such as Nck, the Ras GTPase-activating protein (RasGAP) or the product of the X-lymphoproliferative syndrome gene, SH2D1A/SAP. 3,[6][7][8] The structure of Dok-1 presents some similarities with other adapter molecules such as Gab proteins or insulin receptor substrate (IRS) proteins. 9,10 Two proteins sharing extensive sequence homology with the amino-terminal part (PH and PTB domains) of Dok-1 have been cloned: Dok-2 (also known as FRIP or Dok-R) [11][12][13][14] and Dok-3 (also known as Dok-L).…”

Section: Introductionmentioning

confidence: 99%

DOK4 and DOK5: new dok-related genes expressed in human T cells

et al. 2003

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Dok proteins are adapter proteins involved in signal transduction. Several intracellular proteins expressed in lymphocytes meet the criteria of membrane-associated adapter proteins such as members of the Dok family. To understand the role and the formation of multiprotein networks involving Dok proteins in T lymphocytes, we search for potential additional members of this family. Here, we describe the two new human dok-related genes DOK4 and DOK5 and present data showing the expression of DOK4 and DOK5 genes in T cells. These genes are the orthologues of mouse Dok4 and Dok5 genes. Based on analysis of phylogenetic trees and exon/intron structure of Dok family members, DOK4 and DOK5 define a subfamily within dok genes distinct from DOK1, DOK2 and DOK3. So, Dok-4 and Dok-5 molecules constitute a new group of adapter proteins in T cells, requiring further functional analysis.

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“…For example, Nck binds directly to the ligand-stimulated PDGF receptor-␤ . On the other hand, Nck appears to associate with the activated EGF receptor indirectly via the GTPase-activating protein (GAP)-associated phosphotyrosine protein p62 (Tang et al, 1997). Studies using monoclonal anti-phospholipase C-␥1 antibodies have shown that Nck shares a common epitope with phospholipase C-␥1 (Park and Rhee, 1992;Meisenhelder and Hunter, 1992), and a mouse Nck cDNA has been isolated using an anti-phospholipase C-␥1 monoclonal antibody (Park, 1997).…”

Section: Introductionmentioning

confidence: 99%

Nck-2, a Novel Src Homology2/3-containing Adaptor Protein That Interacts with the LIM-only Protein PINCH and Components of Growth Factor Receptor Kinase-signaling Pathways

1998

MBoC

167

166

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Many of the protein-protein interactions that are essential for eukaryotic intracellular signal transduction are mediated by protein binding modules including SH2, SH3, and LIM domains. Nck is a SH3-and SH2-containing adaptor protein implicated in coordinating various signaling pathways, including those of growth factor receptors and cell adhesion receptors. We report here the identification, cloning, and characterization of a widely expressed, Nck-related adaptor protein termed Nck-2. Nck-2 comprises primarily three Nterminal SH3 domains and one C-terminal SH2 domain. We show that Nck-2 interacts with PINCH, a LIM-only protein implicated in integrin-linked kinase signaling. The PINCHNck-2 interaction is mediated by the fourth LIM domain of PINCH and the third SH3 domain of Nck-2. Furthermore, we show that Nck-2 is capable of recognizing several key components of growth factor receptor kinase-signaling pathways including EGF receptors, PDGF receptor-␤, and IRS-1. The association of Nck-2 with EGF receptors was regulated by EGF stimulation and involved largely the SH2 domain of Nck-2, although the SH3 domains of Nck-2 also contributed to the complex formation. The association of Nck-2 with PDGF receptor-␤ was dependent on PDGF activation and was mediated solely by the SH2 domain of Nck-2. Additionally, we have detected a stable association between Nck-2 and IRS-1 that was mediated primarily via the second and third SH3 domain of Nck-2. Thus, Nck-2 associates with PINCH and components of different growth factor receptor-signaling pathways via distinct mechanisms. Finally, we provide evidence indicating that a fraction of the Nck-2 and/or Nck-1 proteins are associated with the cytoskeleton. These results identify a novel Nck-related SH2-and SH3-domain-containing protein and suggest that it may function as an adaptor protein connecting the growth factor receptor-signaling pathways with the integrin-signaling pathways.

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Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth factor

Cited by 36 publications

References 31 publications

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R

DOK4 and DOK5: new dok-related genes expressed in human T cells

Nck-2, a Novel Src Homology2/3-containing Adaptor Protein That Interacts with the LIM-only Protein PINCH and Components of Growth Factor Receptor Kinase-signaling Pathways

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