Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily.

Bennett, Brian D.; Wang, Zhengyu; Kuang, Wun Jing; Wang, Anlai; Groopman, Jerome E.; Goeddel, David V.; Scadden, David T.

doi:10.1016/s0021-9258(17)36776-5

Cited by 68 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Within this region of homology, T73849 putatively encodes the cytokine receptor motif WSNWS. To obtain full-length cDNA clones, oligonucleotide probes were designed from the EST sequence and used to screen a human fetal liver library and then a library from the hepatoma cell line Hep3B [21]. Sequence information from the resulting cDNAs allowed the amplification of full-length clones from human CD34 + progenitor cells, using the RACE (rapid amplification of cDNA ends) technique.…”

Section: Identification Of Est T73849mentioning

confidence: 99%

A role for leptin and its cognate receptor in hematopoiesis

et al. 1996

View full text Add to dashboard Cite

We have discovered that leptin and its cognate receptor constitute a novel hematopoietic pathway that is required for normal lymphopoiesis. This pathway seems to act at the level of the hematopoietic stem/progenitor cell, and may well also impact upon erythropoiesis, particularly in anemic states that may require output from the spleen. These findings offer a new perspective on the role of the fat cell in hematopoiesis.

show abstract

Section: Identification Of Est T73849mentioning

confidence: 99%

A role for leptin and its cognate receptor in hematopoiesis

et al. 1996

View full text Add to dashboard Cite

show abstract

“…DTX3 E3 Ligase is a representative of the C3CH4 ring group that includes DTX1, DTX2, and DTX3L; have been found to be involved in the regulation of Notch signaling [ 8 , 9 , 10 , 11 , 12 , 13 ]. EphB4 belongs to the family of EphB/Ephrin membrane tyrosine kinases [ 14 , 15 ], which is expressed in arterial endothelial cells during vasculogenesis [ 16 , 17 , 18 , 19 ] and has been found to be overexpressed in malignant cancer cells. It has been associated with a variety of cancer-promoting effects, including morphogenesis, angiogenesis, invasion, and metastasis [ 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Isoform DTX3c Associates with UBE2N-UBA1 and Cdc48/p97 as Part of the EphB4 Degradation Complex Regulated by the Autocrine IGF-II/IRA Signal in Malignant Mesothelioma

Scalia

Merali

Barrero

et al. 2023

IJMS

View full text Add to dashboard Cite

EphB4 angiogenic kinase over-expression in Mesothelioma cells relies upon a degradation rescue signal provided by autocrine IGF-II activation of Insulin Receptor A. However, the identity of the molecular machinery involved in EphB4 rapid degradation upon IGF-II signal deprivation are unknown. Using targeted proteomics, protein–protein interaction methods, PCR cloning, and 3D modeling approaches, we identified a novel ubiquitin E3 ligase complex recruited by the EphB4 C tail upon autocrine IGF-II signal deprivation. We show this complex to contain a previously unknown N-Terminal isoform of Deltex3 E3-Ub ligase (referred as “DTX3c”), along with UBA1(E1) and UBE2N(E2) ubiquitin ligases and the ATPase/unfoldase Cdc48/p97. Upon autocrine IGF-II neutralization in cultured MSTO211H (a Malignant Mesothelioma cell line that is highly responsive to the EphB4 degradation rescue IGF-II signal), the inter-molecular interactions between these factors were enhanced and their association with the EphB4 C-tail increased consistently with the previously described EphB4 degradation pattern. The ATPase/unfoldase activity of Cdc48/p97 was required for EphB4 recruitment. As compared to the previously known isoforms DTX3a and DTX3b, a 3D modeling analysis of the DTX3c Nt domain showed a unique 3D folding supporting isoform-specific biological function(s). We shed light on the molecular machinery associated with autocrine IGF-II regulation of oncogenic EphB4 kinase expression in a previously characterized IGF-II+/EphB4+ Mesothelioma cell line. The study provides early evidence for DTX3 Ub-E3 ligase involvement beyond the Notch signaling pathway.

show abstract

“…They also have well-defined roles in the function of many tissues and organs of the adult body, including regulating nervous system plasticity and blood vessel integrity (1,2). The involvement of Eph receptors and ephrins in cancer formation and progression is also now well-established (3)(4)(5)(6)(7). Recently, ephrin-B1 was shown also to be involved in T-cell activation (8), platelet aggregation (9), and morphogenetic movements of cells during development (10,11).…”

mentioning

confidence: 99%

Crystal Structure of the Ephrin-B1 Ectodomain: Implications for Receptor Recognition and Signaling

Nikolov

Barton

et al. 2005

Biochemistry

View full text Add to dashboard Cite

Eph receptors and their ephrin ligands are involved in various aspects of cell-cell communication during development, including axonal pathfinding in the nervous system and cell-cell interactions of the vascular endothelial cells. Recent structural studies revealed unique molecular features, not previously seen in any other receptor-ligand families, and explained many of the biochemical and signaling properties of Ephs and ephrins. However, unresolved questions remain regarding the potential oligomerization and clustering of these important signaling molecules. In this study, the biophysical properties and receptor-binding preferences of the extracellular domain of ephrin-B1 were investigated and its crystal structure was determined at 2.65 A resolution. Ephrin-B1 is a monomer both in solution and in the crystals, while it was previously shown that the closely related ephrin-B2 forms homodimers. The main structural difference between ephrin-B1 and ephrin-B2 is the conformation of the receptor-binding G-H loop and the partially disordered N-terminal tetramerization region of ephrin-B1. The G-H loop is structurally rigid in ephrin-B2 and adopts the same conformation in both the receptor-bound and unbound ligand, where it mediates receptor-independent homodimerization. In the ephrin-B1 structure, on the other hand, the G-H loop is not involved in any homotypic interactions and adopts a new, distinct conformation. The implications of the ephrin-B1 structure, in context of available ephrin-B1 mutagenesis data, for the mechanism of Eph-ephrin recognition and signaling initiation are discussed.

show abstract

Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily.

Cited by 68 publications

References 34 publications

A role for leptin and its cognate receptor in hematopoiesis

A role for leptin and its cognate receptor in hematopoiesis

Novel Isoform DTX3c Associates with UBE2N-UBA1 and Cdc48/p97 as Part of the EphB4 Degradation Complex Regulated by the Autocrine IGF-II/IRA Signal in Malignant Mesothelioma

Crystal Structure of the Ephrin-B1 Ectodomain: Implications for Receptor Recognition and Signaling

Contact Info

Product

Resources

About