# Regulatory Pathways of SR Protein Kinases

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $323,720

## Abstract

Project Summary/Abstract:
 The splicing of mRNA is a complex biological process that enormously enhances the
diversity of proteins within a limited set of protein-coding genes in the cell. While integral for
normal function, errors in splicing can occur and lead to various diseases including muscular
dystrophy, Alzheimer's disease, parkinsonism, cardiovascular disease, ataxias and cancers.
Splicing relies on essential factors known as SR proteins that bind precursor mRNA and then
selectively incorporate other protein/RNA elements ultimately leading to a macromolecular
machine known as the spliceosome that performs the necessary excision of certain non-coding
elements. The SRPKs are a family of protein kinases that phosphorylate and direct SR
proteins to the nucleus where they participate in these essential splicing functions. Although
much is known about SRPK function in the cytoplasm, less is known about their role in the
nucleus. Furthermore, although SRPKs are best known for their role in splicing, we showed
recently that SRPK1 phosphorylates protamines, thereby regulating protamine-to-histone
exchange on the paternal genome upon fertilization. We will investigate how SRPK1 forms a
complex with a second protein kinase in the nucleus to activate the phosphorylation and
release of SR proteins and the U1 snRNP component U1-70K for splicing function. We will
also explore how SRPK1 uses a novel recognition mechanism compared to SR proteins to
phosphorylate protamines and induce DNA phase transitions and genomic decondensation
necessary for oocyte development. These studies will involve a broad range of biophysical
and biological techniques including mass spectrometry, molecular and cell biology, enzyme
kinetics, and confocal microscopy. Overall, the experiments outlined in this proposal will
address the key functions of the protein kinase SRPK1 in controlling protein diversity as well
as at the earliest stages of life.

## Key facts

- **NIH application ID:** 10297467
- **Project number:** 2R01GM067969-17A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** JOSEPH ADAMS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,720
- **Award type:** 2
- **Project period:** 2004-02-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297467

## Citation

> US National Institutes of Health, RePORTER application 10297467, Regulatory Pathways of SR Protein Kinases (2R01GM067969-17A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10297467. Licensed CC0.

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