# Eph Receptor Heterointeractions in Signaling

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2023 · $511,800

## Abstract

SUMMARY
Receptor tyrosine kinases (RTKs) can interact with other members of the same RTK family, forming
heterocomplexes with distinctive signaling activities that have both physiological and pathogenic relevance.
These heterointeractions likely occur within each of the 20 RTK families, but they have not been studied in
most cases. The Eph family, with 14 members, is the largest of the receptor tyrosine kinase families. Different
Eph receptors are often expressed in the same cells, and some evidence suggests that these co-expressed
Eph receptors can form heterocomplexes. Among the Eph receptors, EphA2 is the one most profoundly linked
to disease. EphA2 signaling is complex because it can mediate diverse, and often opposite, biological
functions. For example, EphA2 can exert either anti-oncogenic or pro-oncogenic effects through different
ligand-dependent and ligand-independent signaling mechanisms. Although heterointeractions with other co-
expressed Eph receptors likely contribute to the versatility of EphA2 signaling and to the pathological effects of
EphA2, the significance of these interactions is not well understood. In this proposal, we seek to enhance our
basic knowledge about the biological significance of EphA2 heterointeractions through the use of innovative
tools and experimental approaches. In Aim 1, we will use quantitative biophysical strategies that we have
developed to characterize ligand-independent interactions of EphA2 with other Eph receptors. In Aim 2, we will
characterize EphA2 interactions with other Eph receptors in the presence of an EphA2-specific ligand. In Aim
3, we will define the functional consequences of specific heterointeractions for EphA2 signaling. This will be
accomplished by investigating the effects of heterointeractions on EphA2 phosphorylation, effector recruitment,
downstream signaling pathways, and cellular responses impacting cell migration/invasion. This work will
identify mechanisms by which interacting Eph receptors affect EphA2-mediated signaling processes. This in
turn will inform the design of future therapies targeting mixed EphA2-Eph signaling platforms.

## Key facts

- **NIH application ID:** 10658732
- **Project number:** 2R01GM131374-05
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Kalina Hristova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $511,800
- **Award type:** 2
- **Project period:** 2019-01-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10658732

## Citation

> US National Institutes of Health, RePORTER application 10658732, Eph Receptor Heterointeractions in Signaling (2R01GM131374-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10658732. Licensed CC0.

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