Embryonic stem cells express multiple Eph-subfamily receptor tyrosine kinases.

Abstract

Eph and its homologues form the largest subfamily of receptor tyrosine kinases. Normal expression patterns of this subfamily indicate roles in differentiation and development, whereas The receptor tyrosine kinases (RTKs) are transmembrane molecules which transduce signals from the extracellular environment into the cytoplasm. They include well-studied regulators of cell proliferation and differentiation, such as c-Kit and the receptors for epidermal growth factor, platelet-derived growth factor, and macrophage colony-stimulating factor (1). Signaling by an RTK is initiated when its ligand binds to the extracellular domain of the receptor. This leads to the formation of receptor dimers, which activate their catalytic domains by reciprocal phosphorylation on tyrosine residues (2). Once activated, RTKs can bind and phosphorylate specific intracellular proteins that act as second messengers.

Deciphering the signaling events that promote melanoma tumor cell vasculogenic mimicry and their link to embryonic vasculogenesis: Role of the Eph receptors

“…These data revealed a dysregulated genotype whereby highly aggressive melanoma tumor cells expressed various endothelial and epithelial genes important for both embryonic vasculogenesis and angiogenesis, including many different Eph receptors and ligands (Table 1; Bittner et al, 2000;Seftor et al, 2002). Given the role of the Eph receptors and their ligands in mediating many aspects of embryonic development combined with reports identifying the expression of multiple Eph-family receptor tyrosine kinases in human and mouse embryonic stem cells (Baharvand et al, 2006;Lickliter et al, 1996) as well as in hematopoietic stem cells (Lazarova et al, 2006) suggested that the aggressive melanoma tumor cells had undergone transdifferentiation to acquire a more embryonic-like phenotype. These data, in combination with data supporting a role for Eph receptors in embryonic vasculogenesis as well as angiogenesis, suggest that expression of these Eph receptors and ligands are playing a role in mediating melanoma VM.…”

EphA2 overexpression promotes ovarian cancer growth

“…[1][2][3][4] It is expressed in its active phosphorylated form in organs with a high proportion of epithelial cells such as skin, intestine and lung. 1,5,6 For oncology applications, interest in EphA2 has grown recently due to its increased expression in most cancers including lung, breast, ovary, prostate, colorectal, skin and esophagus. [7][8][9][10][11][12][13] Interestingly, EphA2 is located on chromosome 1p36.1, which is a hotspot for rearrangements in many human cancers including ovarian cancer.…”

Ephrin B2 Induces T Cell Costimulation

“…For example, EphA1 (11), EphA2 (12), EphA3, EphA4 (13), EphB2 (14), EphB4 (15), and EphB6 (16) are expressed in the thymus; EphB6 is expressed on mature T cells (17,18); EphA3 is expressed in pre-B cell lines (11), and EphA4 and EphA7 are significantly expressed in B cells (19); EphA2 (19) and EphB1 (20) are expressed in certain types of dendritic cells; and some Ephs, such as EphA3 (21), EphB4 (22), and EphB6 (18,23), are expressed in leukemia cells. As for EFNs, EFNA1 (24), EFNA3, EFNB1 (25), EFNA2, EFNA4, and EFNA5 (13) are expressed in the thymus; EFNA4 can be detected in peripheral T and B cells (19).…”