# Regulation of Syk Expression in Human Basophils

> **NIH NIH R56** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

Abstract:
Immediate hypersensitivity reactions are dependent on IgE-mediated activation of basophils and mast cells.
There are many elements that regulate expression of the response that distribute up and down the cascade of
events from the generation of IgE to the tissue end-organ response and the positive and negative feedback
loops that link the various elements together. One of the early necessary elements is related to the intrinsic
ability of the basophil and mast cell to respond to aggregation of the IgE receptor. It is now apparent that for
human basophils, this intrinsic responsiveness primarily relates the expression of one of the early receptor
associated kinases, SYK. Several studies have established that SYK activity is likely a rate-limiting step in the
IgE-dependent signal transduction cascade and expression levels determine its activity. Studies have also
demonstrated that the very low expression levels of SYK in basophils are unique to this leukocyte. Recent
studies demonstrate 4 regulatory pathways of SYK expression, two of which have recently been excluded for
further consideration. Based on preliminary results, the application proposes to examine two new pathways in
greater detail, one extrinsic and one intrinsic, modulation by SCF/Flt3 and basophil-specific differentiation
transcription factors, respectively. Aim 1 of the proposal will refine pilot study observations on how Flt3L and
SCF down-regulate SYK expression in maturing basophils. Aim 2 will validate preliminary results that suggest
that c-MAF, KLF4 and/or ZNF608 regulate transcription of SYK at one of 3 regions of the SYK gene. Aim 3 will
extend the results of aim 2 to the human mast cell, testing whether regulation of SYK by the transcriptional
control discovered for basophils operates in mast cells.

## Key facts

- **NIH application ID:** 10123751
- **Project number:** 1R56AI139326-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Donald W MacGlashan
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123751

## Citation

> US National Institutes of Health, RePORTER application 10123751, Regulation of Syk Expression in Human Basophils (1R56AI139326-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10123751. Licensed CC0.

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