# Understanding Ras effector switching and roles of Ras>RalGEF>Ral in development

> **NIH NIH R35** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $374,881

## Abstract

SUMMARY
Ras is the most mutated oncoprotein and functions at the center of an evolutionarily conserved
network of proteins mutated in the RASopathy spectrum of heritable developmental disorders.
Certain facets of Ras biology, like signaling cascades downstream of the Raf and PI3K oncogenic
effectors, are among the best studied and pharmacologically targeted signals in all of biology. Yet
how Ras switches between different effectors and the roles of the oncogenic RalGEF>Ral effector
during development are poorly understood due to paralog redundancy, technical limitations in
more complex systems, and the roadblock of Ral using the exocyst complex as a signaling
intermediary. Research in this laboratory focuses on understanding the composition,
organizational principles, and functions of signal transduction networks in vivo. This proposal will
support a series of projects to answer how Ras switches between effectors in different
developmental contexts, explore unexpected signaling relationships with other characterized
signaling cascades, untangle the apparently paradoxical relationship between Ral and the
exocyst complex in signaling vs. exocytosis, and to identify and understand novel functions of
RalGEF>Ral signaling in development and physiology, about which surprisingly little is known.
The laboratory has developed several crucial technical advances to overcome barriers to
progress in this field. The proposed projects build on the lab’s ability dissect complex webs of
signal transduction using genetic principles, complemented by cell biological and biochemical
approaches. The proposed research is reasonably expected to discover novel principles and
components in signal transduction.

## Key facts

- **NIH application ID:** 10330868
- **Project number:** 1R35GM144237-01
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** David Reiner
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $374,881
- **Award type:** 1
- **Project period:** 2022-01-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330868

## Citation

> US National Institutes of Health, RePORTER application 10330868, Understanding Ras effector switching and roles of Ras>RalGEF>Ral in development (1R35GM144237-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10330868. Licensed CC0.

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