# Atypical MAP Kinase Signal Transduction

> **NIH NIH R15** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2022 · $436,243

## Abstract

Project Summary:
 MAP kinases (MAPKs) are regulatory components of many signal transduction
pathways that impact eukaryotic cell growth, differentiation, and movement. Relatively
little is known about the function and regulation of atypical MAPKs (represented by
MAPK15/Erk8 in mammals) found only in eukaryotes that have cell motility. Atypical
MAPKs are not activated by conventional MAPK kinases and the external signals that
trigger activation are not known except in the amoeba Dictyostelium, a model organism
for chemotactic movement and development. We have found that the Dictyostelium
atypical MAPK, Erk2, is essential for chemotactic movement to multiple signals. In our
previously funded research we also discovered that Erk2 phosphorylates specific
residues of a GATA transcription factor, GtaC, resulting in the translocation of this factor
from the nucleus to the cytoplasm in response to at least two chemotactic signals that
promote different cell fates. We have also demonstrated that Erk2 kinase activity is not
required for activation in vivo indicating that an unconventional MAPK kinase regulates
atypical MAPKs rather than autophosphorylation. The proposed research will
investigate if Erk2 promotes different cell fates through the differentially modification of
GtaC or through the regulation of other transcription factors. We will use a GFP tagged
GtaC to map Erk2 docking sites and compare these to docking sites of other groups of
MAPKs. We will also use co-immunoprecipitations, mass spectrometry, and genetic
analysis to identify proteins that associate and function with Erk2 in signaling pathways
and identify proteins that directly regulate Erk2 activation. The results of this project are
expected to identify specific mechanisms of atypical MAPK regulation and function and
uncover roles for atypical MAPK signaling in chemotactic movement and cell fate
determination that can guide the research of MAPKs in other organisms such as
mammals.

## Key facts

- **NIH application ID:** 10577709
- **Project number:** 2R15GM131269-02
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** JEFFREY A HADWIGER
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $436,243
- **Award type:** 2
- **Project period:** 2019-03-08 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10577709

## Citation

> US National Institutes of Health, RePORTER application 10577709, Atypical MAP Kinase Signal Transduction (2R15GM131269-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10577709. Licensed CC0.

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