EPHA1

Official Full Name

EPH receptor A1

Organism

Homo sapiens

GeneID

2041

Background

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene is expressed in some human cancer cell lines and has been implicated in carcinogenesis. [provided by RefSeq, Jul 2008]

Synonyms

EPH; EPHT; EPHT1;

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Detailed Information

EphA1 is the first member of a subfamily Eph family of receptor tyrosine kinases. It is not only involved in embryonic development and angiogenesis, but also widely expressed in normal adult tissues. Its unique structure characteristics and signal transduction patterns of receptor and ligand complexes have attracted more and more attention in tumor development and metastasis. In different organs, different types of tumors, and even at different stages of the same tumor development, the expression status of EphA1 gene is also very different, suggesting the diversity of the function of the gene.

EphrinA1 and EphrinA3 are high-affinity ligands for EphA1, which are anchored to the cell membrane by a glycosylphosphatidylinositol chain and bind to the globular domain outside the membrane of EphA1. They transmit signals to the cell membrane, causing phosphoric acid of tyrosine residues. Finally, they stimulate signaling proteins such as Grb2, Grb10, Nck and RasGTPase2 activator proteins bind to the SAM region and transmit signals to downstream proteins, regulating embryonic development, angiogenesis, tumorigenesis and metastasis.

Expression of EphA1

EphA1 is widely expressed in animal tissues and is found in sponges, fruit flies, new rod-shaped nematodes, rats, chickens, mice, and humans. This gene participates in axon guidance, synapse formation and cell proliferation, adhesion, migration and angiogenesis in embryonic development. EphA1 also participates in the process of learning and memory, and has important physiological functions. Gene expression of EphA1 and its two high-affinity ligands ephrinA1 and ephrinA3 are involved in early fetal gastrula, neuroblast and somite formation, and early organ development in fetal rats. Signal transduction between EphA1 and ligands regulates cell rejection and adhesion. Moreover, this signal transduction plays a key role in establishing, maintaining and remodeling cell morphology.

EphA1 is not only involved in embryonic development, but also widely expressed in normal adult tissues. The expression of 21 Eph receptors and ligands in adult skin and 13 other normal adult tissues was studied by real-time quantitative PCR. EphA1 was found to be the lowest expressed in the bone marrow, low in the uterus, spleen, brain and testis, and gradually increased in the prostate, lung, etc., and highest in the bladder and skin, especially in the epidermis.

In the late stage of inflammation, the expression of EphA1 in lymphocytes and vascular endothelial cells is reduced, causing an increase in adhesion between lymphocytes and endothelial cells, which leads to extravasation of lymphocytes and tissue migration.

Figure 1. structural elements of an Eph receptor and ephrin ligands. (Shiuan, et al. 2016)

EphA1 and Tumor

The receptor tyrosine kinase EphA1 gene has been shown to be involved in the development, progression, and invasion of a variety of tumors. The study found that EphA1 mRNA is overexpressed in advanced ovarian cancer. Wong et al. used genome-wide expression microarray analysis to find that EphA1 is abnormally expressed in epithelial ovarian cancer. The level of transcriptional expression of EphA1 in normal prostate, primary and metastatic prostate cancer cell lines is progressively decreased, indicating that EphA1 is involved in the malignant transformation process that prevents normal prostate cell phenotype.

EphA1 expression levels and clinical parameters of the tumor such as tumor stage, grade, metastasis and prognosis are rarely involved. As a potential prognostic indicator and a promising new therapeutic target, future research on the structure and function of EphA1 and its relationship with clinical parameters of cancer patients will open up new ideas for the prevention and treatment of tumors.

References:

Shiuan, E., & Jin, C. (2016). Eph receptor tyrosine kinases in tumor immunity. Cancer Research, 76(22).
Wong, Y. L., Dali, A. Z., Mohamed, R. I., Jamal, R., & Mokhtar, N. M. (2016). Potential molecular signatures in epithelial ovarian cancer by genome wide expression profiling. Asia Pac J Clin Oncol, 12(2), e259-e268.
Nguyen, T. M., Arthur, A., & Gronthos, S. (2015). The role of eph/ephrin molecules in stromal–hematopoietic interactions. International Journal of Hematology, 103(2), 1-10.

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