Tyrosine 1213 of Flt-1 Is a Major Binding Site of Nck and SHP-2

Igarashi, Katsuhide; Isohara, Toshio; Kato, Toshiaki; Shigeta, Keiko; Yamano, Tomoka; Uno, Isao

doi:10.1006/bbrc.1998.8578

Cited by 56 publications

(31 citation statements)

References 11 publications

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“…A fusion of the intracellular domain of Flt1 with the GAL4-BD interacted with fusions of PI 3-kinase, Nck, SHP-2, and PLC␥ with the GAL4-AD (47,48). In Flt1, tyrosine 794 in the juxtamembrane region, as well as tyrosine 1169, in the C-terminal tail, interacted with the N-terminal SH2 domain of PLC␥ (35).…”

Section: Discussionmentioning

confidence: 99%

Utilization of Distinct Signaling Pathways by Receptors for Vascular Endothelial Cell Growth Factor and Other Mitogens in the Induction of Endothelial Cell Proliferation

Wu¹,

Mayo²,

Dunbar³

et al. 2000

Journal of Biological Chemistry

265

197

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Section: Discussionmentioning

confidence: 99%

Utilization of Distinct Signaling Pathways by Receptors for Vascular Endothelial Cell Growth Factor and Other Mitogens in the Induction of Endothelial Cell Proliferation

Wu¹,

Mayo²,

Dunbar³

et al. 2000

Journal of Biological Chemistry

265

197

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“…They are located in the C-terminal tail domain and may serve as docking sites for signaling molecules such as PLCg, Nck, Crk, SHP-1/2, or the p85 subunit of PI3 kinase, as shown by yeast two hybrid assays and by in vitro binding studies (Cunningham et al, 1995;Igarashi et al, 1998a). Activation of PLCg and RasGAP has been reported in VEGFR-1 transfected ®broblasts (Seetharam et al, 1995).…”

Section: Vegfr-1mentioning

confidence: 99%

Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis

2000

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“…Stimulation of bovine aortic endothelial cells (BAEC) with VEGF increased tyrosine phosphorylation of Nck and its association with PI-3K and a complex containing GAP, p190RhoGAP and p62 dok (Guo et al, 1995). Nck binds directly to the activated VEGFR-1 at both Y-1213 and Y-1333 (Igarashi et al, 1998) and also to activated VEGFR-2/KDR (Kroll and Waltenberger, 1997). Stoletov and colleagues have recently shown that VEGF stimulation recruited the Nck-Pak complex to focal adhesions, and the Nck-Pak complexed with FAK in human umbilical vein endothelial cells (HUVE).…”

Section: Nck Links Cell Surface Receptors To the Actin Cytoskeletonmentioning

confidence: 99%

Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton

2001

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In response to extracellular signals, cell surface receptors engage in connections with multiple intracellular signaling pathways, leading to the cellular responses such as survival, migration, proliferation and di erentiation. Thè pY?SH2/SH3?e ector' connection is a frequently used scheme by many cell surface receptors, in which SH2/SH3-containing adapters connect protein tyrosine phosphorylation to a variety of downstream e ector pathways. Following the initial landmark ®nding that Grb2 adapter links the receptors to the Ras pathway leading to DNA synthesis, recent studies have revealed that the biological function of the SH2/SH3 adapter Nck/Dock is to link cell surface receptors to the actin cytoskeleton. For example, in the evolutionarily-conserved signaling network, GEF-Rac-Nck-Pak, Nck`®xes up' the interaction of Pak with its upstream activator, Rac. The activated Pak then regulates the cytoskeletal dynamics. The fact that the majority of the more than 20 Nck-SH3-associated e ectors are regulators of the actin cytoskeleton suggests that Nck/Dock regulates, via binding to distinct e ectors, various cell type-speci®c motogenic responses. This review focuses on our current understanding of Nck/Dock function. Due to the number and complexity of the terminologies used in this review, à Glossary of Terms' is provided to help reduce confusions. Oncogene (2001) 20, 6403 ± 6417.Keywords: Src-homology domains; adapters; tyrosine kinases; signal transduction; cytoskeleton The SH2/SH3 adapters The src-homology 2 (SH2) and src-homlogy 3 (SH3) domains are protein ± protein interaction modules, found in a variety of structurally and functionally distinct signaling molecules, including protein tyrosine kinases/phosphatases, lipid kinase/phosphatase, guanine nucleotide exchange factors/GTPase activation proteins, docking proteins/adapters, cytoskeletal binding proteins and even transcription factors (Pawson, 1995;Mayer, 1999). Except for the terminology, SH2 and SH3 domains share no other common features regarding their structures, binding speci®city, and cellular targets. SH2 domains enable their host proteins to form complexes with phosphotyrosine (pY) proteins by binding to pY residues within these proteins. The stability and speci®city of the binding also depend upon the additional three to six amino acid residues immediately carboxyl to the pY residue, pY-(X) 3 ± 6 . Therefore, SH2 domains from di erent host molecules bind di erent pY-containing peptides. SH3 domains bind proline-rich segments of target molecules with a minimum consensus of P-x-x-P (Mayer, 2001). Each proline is often preceded by an aliphatic amino acid residue, and the aliphatic-proline pair binds to a hydrophobic pocket on SH3 domains. A major di erence between the SH2-pY binding and SH3-PxxP interactions is that the former is always transiently induced by extracellular signals, whereas the latter is often, but not always, constitutive. For instance, the SH2 domain of the adapter protein Grb2 only binds to tyrosine phosphorylated/activated EGFR, whe...

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Tyrosine 1213 of Flt-1 Is a Major Binding Site of Nck and SHP-2

Cited by 56 publications

References 11 publications

Utilization of Distinct Signaling Pathways by Receptors for Vascular Endothelial Cell Growth Factor and Other Mitogens in the Induction of Endothelial Cell Proliferation

Utilization of Distinct Signaling Pathways by Receptors for Vascular Endothelial Cell Growth Factor and Other Mitogens in the Induction of Endothelial Cell Proliferation

Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis

Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton

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