Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system.

Sato, Thomas N.; Qin, Ying; Kozak, Christine A.; Audus, Kenneth L.

doi:10.1073/pnas.90.20.9355

Cited by 415 publications

(246 citation statements)

References 26 publications

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“…Several studies have suggested that the Tie protein plays an important role in angiogenesis Sato et al, 1993;Korhonen et al, 1994Korhonen et al, , 1995. In recent studies high amounts of Tie mRNA and also Tie protein have been detected in human brain tumours in contrast to the less abundant expression of Tie mRNA or protein in the respective normal brain tissue control samples (Kaipainen et al, 1994;Hatva et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Tie and Tek (Dumont et al, 1993) are members of a new subfamily of endothelial cell RTKs whose extracellular domains contain three different types of structural motifs: immunoglobulin (Ig)-like loops, cysteine-rich epidermal growth factor (EGF)-like domains and fibronectin type III (FN III) domains (Maisonpierre et al, 1993;Sato et al, 1993;Ziegler et al, 1993).…”

mentioning

confidence: 99%

“…Tie mRNA is especially prominent in endothelial cells during embryonic angiogenesis (Sato, et al, 1993;Dumont, et al, 1993;Korhonen et al, 1992Korhonen et al, , 1994Korhonen et al, , 1995. Disruption of the Tie gene locus by targeted mutagenesis was lethal.…”

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confidence: 99%

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Endothelial Tie growth factor receptor provides antigenic marker for assessment of breast cancer angiogenesis

Salvén

Joensuu²,

Heikkilä³

et al. 1996

Br J Cancer

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Summary Breast cancer prognosis has previously been linked to the degree of tumour vascularisation. In order to establish additional markers for tumour angiogenesis, we have used monoclonal antibodies against the endothelial Tie receptor tyrosine kinase to study the degree of vascularisation of breast carcinomas and the regulation of Tie expression in the vascular endothelial cells. Antibodies were used for Tie detection and the results were correlated with other prognostic markers. Of four monoclonal antibodies directed against different epitopes of the Tie extracellular domain, two reacted against Tie in unfixed histopathological sections of breast carcinomas. One of these antibodies (clone 7e8) was specific for the endothelial cells whereas the other (clone 10fl 1) also reacted with basement membranes and occasional carcinoma cells. When Tie expression was studied with the antibody clone 7e8, all 27 carcinomas, two in situ carcinomas, samples of histologically normal breast tissue (n = 16) or normal skin or lymph node tissue (n= 5) showed staining. Microvessel counts were higher in carcinomas (median 14; range 3 -27) than in fibrodenomas (median 10; range 5 -18) or histologically normal breast tissue (median 7; range 3 -15, P = 0.0006). A similar result was obtained using antibodies against the CD31 (PECAM) antigen. Microvessel counts in 7e8 staining were not significantly associated with primary tumour size, axillary nodal status, histological grade or staining for oestrogen receptor, progesterone receptor, Ki-67 proliferation marker or p53 oncoprotein.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Endothelial Tie growth factor receptor provides antigenic marker for assessment of breast cancer angiogenesis

Salvén

Joensuu²,

Heikkilä³

et al. 1996

Br J Cancer

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“…Similar to VEGF, the specificity of the Ang for the vascular endothelium results from the restricted distribution of their receptors, Tie1 and Tie2, to these cells. Tie1 and Tie2 are also receptor tyrosine kinases (Sato et al, 1993). All the known Ang bind primarily to Tie2 and it is unclear whether there are independent ligands for the second Tie receptor, Tie1.…”

Section: Angiopoietinsmentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

614

429

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Endothelial cells play a wide variety of critical roles in the control of vascular function. Indeed, since the early 1980s, the accumulating knowledge of the endothelial cell structure as well as of the functional properties of the endothelial cells shifted their role from a passive membrane or barrier to a complex tissue with complex functions adaptable to needs specific in time and location. Hence, it participates to all aspects of the vascular homeostasis but also to physiological or pathological processes like thrombosis, inflammation, or vascular wall remodeling. Some of the most important endothelial functions will be described in the following review and more specifically, their role in blood vessel formation, in coagulation and fibribolysis, in the regulation of vascular tone as well as their participation in inflammatory reactions and in tumor neoangiogenesis. J. Cell. Physiol. 196: 430–443, 2003. © 2003 Wiley‐Liss, Inc.

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“…The Tek receptor is ®rst expressed around day 7.5 during mouse development, and it is expressed by endothelial precursors and by the endothelium of actively growing blood vessels (Dumont et al, 1992;Sato et al, 1993). Tek has recently been shown to be expressed at relatively high levels in the quiescent vasculature of a number of adult tissues as well as in healing skin wounds (Wong et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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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Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system.

Cited by 415 publications

References 26 publications

Endothelial Tie growth factor receptor provides antigenic marker for assessment of breast cancer angiogenesis

Endothelial Tie growth factor receptor provides antigenic marker for assessment of breast cancer angiogenesis

Endothelial cell functions

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

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