# Regulatory Pathways of SR Protein Kinases

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $317,750

## Abstract

Project Summary/Abstract:
 Splicing converts a single gene into multiple unique mRNA fragments to expand the
size of the proteome and regulate cell function. While splicing is integral for normal function in
complex organisms, mistakes in splice-selection can lead to disease. In fact, splicing errors
are associated with numerous human disorders including muscular dystrophy, Alzheimer's
disease, parkinsonism, cardiovascular disease, ataxias and cancers. Splicing occurs at the
spliceosome, a macromolecular complex that includes both RNA and protein. In the latter
group, SR proteins are essential splicing factors that control where the spliceosome assembles
on precursor mRNA. SR proteins contain C-terminal domains rich in arginine-serine repeats
whose polyphosphorylation controls splice-site selection. The SRPK family of protein kinases
phosphorylates these RS domains directing SR proteins into the nucleus for splicing activity.
While SRPKs are normally localized to the cytoplasm for this function, they can enter the
nucleus under certain conditions but their function in this cellular compartment is not well
understood. We will now investigate the functions of SRPKs in both the cytoplasm and
nucleus using genome-wide splicing assays, cell imaging, fast-mixing kinetics, protease
footprinting and structural techniques. We will determine how the unique SRPK
phosphorylation mechanism governs transport of SR proteins from the cytoplasm to the
nucleus. We will explore factors that regulate SRPK nuclear import through a novel kinase-
kinase complex. Finally, we will investigate how this complex affects splicing reactions through
the mobilization of SR proteins in the nucleus. Overall, the studies outlined in this proposal will
greatly expand our knowledge of SRPK-induced phosphorylation of SR proteins and their
splicing function.

## Key facts

- **NIH application ID:** 9856454
- **Project number:** 5R01GM067969-16
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** JOSEPH ADAMS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $317,750
- **Award type:** 5
- **Project period:** 2004-02-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856454

## Citation

> US National Institutes of Health, RePORTER application 9856454, Regulatory Pathways of SR Protein Kinases (5R01GM067969-16). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9856454. Licensed CC0.

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