Sck Interacts with KDR and Flt-1 via Its SH2 Domain

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

doi:10.1006/bbrc.1998.9442

Cited by 35 publications

(21 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings also imply that, in addition to its E3 ligase activity, the C-terminal domain of c-Cbl encompassing amino acids 358-906 is critical for regulation of PLC␥1 activity. Recent work has indicated that p85/PI3K (18), PLC␥1 (3,4), Shb (19), and Sck (20,21) are directly recruited to this site. Ultimately, c-Cbl-mediated ubiquitylation and down-regulation of PLC␥1 could enhance the direct recruitment of other binding partners to this site and skew the balance among other biological signals transmitted by VEGFR-2 via pY1173.…”

Section: Discussionmentioning

confidence: 99%

A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCγ1 activation and angiogenesis

Singh

Meyer

Navruzbekov

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCγ1 activation and angiogenesis

Singh

Meyer

Navruzbekov

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

“…Akt also regulates nitric oxide (NO) production by direct phosphorylation and activation of endothelial NO synthase (eNOS). Finally, phosphorylated Tyr1175 is known to interact with Sck (Igarashi et al, 1998;Sakai et al, 2000), an adaptor molecule that binds Grb2, and participates in MAPK signaling in the epidermal growth factor pathway (Thelemann et al, 2005).…”

Section: Vegf Signalingmentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

626

527

View full text Add to dashboard Cite

Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

show abstract

“…Of the remaining tyrosine residues in the intracellular domain of VEGFR-3, five are located in the first and second parts of the kinase domain, and three are located in the juxtamembrane domain (Tyr-812, -830 and -833). Tyrosine residues at positions conserved relative to Tyr-812 are found both in VEGFR-1 (Tyr-794) and VEGFR-2 (Tyr-801) (29). All three VEGFR-3 juxtamembrane tyrosine residues are contained within the same tryptic peptide.…”

Section: Vegfr-3 Tyrosine Phosphorylation Sitesmentioning

confidence: 99%

Ligand-induced Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) Heterodimerization with VEGFR-2 in Primary Lymphatic Endothelial Cells Regulates Tyrosine Phosphorylation Sites

Dixelius

Mäkinen

Wirzenius

et al. 2003

Journal of Biological Chemistry

235

194

View full text Add to dashboard Cite

Vascular endothelial growth factors (VEGFs) regulate the development and growth of the blood and lymphatic vascular systems. Of the three VEGF receptors (VEGFR), VEGFR-1 and -2 are expressed on blood vessels; VEGFR-2 is found also on lymphatic vessels. VEGFR-3 is expressed mainly on lymphatic vessels but it is also up-regulated in tumor angiogenesis. Although VEGFR-3 is essential for proper lymphatic development, its signal transduction mechanisms are still incompletely understood. Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the VEGFR-3 carboxyl-terminal tail. These sites were used both in VEGFR-3 overexpressed in 293 cells and when the endogenous VEGFR-3 was activated in lymphatic endothelial cells. Interestingly, VEGF-C stimulation of lymphatic endothelial cells also induced the formation of VEGFR-3/VEGFR-2 heterodimers, in which VEGFR-3 was phosphorylated only at three of the five sites while the two most carboxyl-terminal tyrosine residues appeared not to be accessible for the VEGFR-2 kinase. Our data suggest that the carboxyl-terminal tail of VEGFR-3 provides important regulatory tyrosine phosphorylation sites with potential signal transduction capacity and that these sites are differentially used in ligand-induced homoand heterodimeric receptor complexes.

show abstract

Sck Interacts with KDR and Flt-1 via Its SH2 Domain

Cited by 35 publications

References 17 publications

A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCγ1 activation and angiogenesis

A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCγ1 activation and angiogenesis

Vascular endothelial growth factor in eye disease

Ligand-induced Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) Heterodimerization with VEGFR-2 in Primary Lymphatic Endothelial Cells Regulates Tyrosine Phosphorylation Sites

Contact Info

Product

Resources

About