Epha2

Case study 1: Zhongwen Chen, 2021

Clustering of ligand:receptor complexes on the cell membrane is widely presumed to have functional consequences for subsequent signal transduction. However, it is experimentally challenging to selectively manipulate receptor clustering without altering other biochemical aspects of the cellular system. Here, the researchers develop a microfabrication strategy to produce substrates displaying mobile and immobile ligands that are separated by roughly 1 μm, and thus experience an identical cytoplasmic signaling state, enabling precision comparison of downstream signaling reactions. Applying this approach to characterize the ephrinA1:EphA2 signaling system reveals that EphA2 clustering enhances both receptor phosphorylation and downstream signaling activity. Single-molecule imaging clearly resolves increased molecular binding dwell times at EphA2 clusters for both Grb2:SOS and NCK:N-WASP signaling modules.

Fig1. Representative immunofluorescence images of EphA2 in MDA-MB-231 cells fixed after 45 min spread on the substrate. The yellow square marked region is enlarged in bottom panel.

Fig2. EphA2 clustering increases Grb2 and N-WASP dwell time in COS7 cells. Representative live-cell images of Grb2-tdEOS or N-WASP-mEOS3.2 transfected COS7 cells spreading on the hybrid substrate.

Case study 2: Zicong Gao, 2021

Tumor metastasis induced by drug resistance is a major challenge in successful cancer treatment. Nevertheless, the mechanisms underlying the pro-invasive and metastatic ability of drug resistance remain elusive. Exosome-mediated intercellular communications between cancer cells and stromal cells in tumor microenvironment are required for cancer initiation and progression. Recent reports have shown that communications between cancer cells also promote tumor aggression. However, little attention has been regarded on this aspect.

Quantitative proteomic analysis showed that EphA2 was rich in exosomes from drug-resistant cells. Exosomal EphA2 conferred the invasive/metastatic phenotype transfer from drug-resistant cells to sensitive cells. Moreover, exosomal EphA2 activated ERK1/2 signaling through the ligand Ephrin A1-dependent reverse pathway rather than the forward pathway, thereby promoting breast cancer progression. Theses findings indicate the key functional role of exosomal EphA2 in the transmission of aggressive phenotype between cancer cells that do not rely on direct cell-cell contact.

Fig3. The expression of EphA2, ABCB1 (encode P-glycoprotein) in exosomes, and cell lysates were analyzed by using Western blotting; β-actin was used as the loading control.

Fig4. ELISA assays showed that the concentration of exosomal EphA2 in plasma was collected from healthy donors (n = 20), early-stage breast cancer patients without any systemic treatment (n = 30), and advanced patients received at least one prior line of systemic therapy (n = 30).

Fig1. Function and regulation of EphA2 in breast cancer and its targeting therapeutics. (Ping Zhao, 2021)

Fig2. Biological and biochemical pathways linked with EphA2. (Jennifer Walker-Daniels, 2003)

Epha2 involved in several pathways and played different roles in them. We selected most pathways Epha2 participated on our site, such as Arf6 signaling events, Axon guidance, Developmental Biology, which may be useful for your reference. Also, other proteins which involved in the same pathway with Epha2 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Epha2 has several biochemical functions, for example, ATP binding, ephrin receptor activity, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Epha2 itself. We selected most functions Epha2 had, and list some proteins which have the same functions with Epha2. You can find most of the proteins on our site.

Epha2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Epha2 here. Most of them are supplied by our site. Hope this information will be useful for your research of Epha2.

EFNA1; EPHA7; HSP90AB1; PTK2; saicar; PKM; PTPN11; KPNA3