# Deciphering the role of low complexity domains in dual specificity kinase function

> **NIH NIH R03** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $158,308

## Abstract

Project Summary
 Dual specificity protein kinases perform indispensable roles in eukaryotes including the
regulation of signal transduction pathways and subcellular compartmentalization. Structurally, in
addition to their folded kinase domains, they are composed of significantly long segments that are
intrinsically disordered. Whereas the folded domains of these kinases are studied extensively
(both biochemically and structurally), little is known about the functional role of the disordered
domains that display a compositional bias towards polar and charged amino acids.
 In our preliminary sequence analysis of all human dual specificity kinases, we identify that
CLK3 has the longest intrinsically disordered region. Recent advances indicate that CLK3 is linked
to multiple cancer pathologies and celiac disorders. For example, overexpression of CLK3 is
associated with osteosarcoma, liver cancer and bile cancer. Sequence variations in CLK3 gene
is associated with bladder cancer, Crohn’s disease and multiple celiac disorders. Functionally,
CLK3 is recruited to nuclear speckles and plays vital roles in the regulation of pre-mRNA splicing.
 In this grant application, we propose to characterize the sequence determinants, molecular
codes and functional roles of CLK3 nuclear speckle recruitment utilizing a combination of in vitro
and in vivo experiments. Based on our preliminary analyses, we posit that (i) the low-complexity
disordered domain of CLK3 (residue 1-285) drives the protein’s nuclear speckle localization, and
(ii) alterations in CLK3 speckle localization/dynamics is associated with disease pathologies. We
will test these hypotheses utilizing an integrative biophysical, biochemical and cell biology
approach. To this end, we will utilize a splice variant, a disease-linked mutant, and rationally
perturbed LCD variants to systematically decipher the LCD’s role in CLK3’s function/dysfunction.
Successful completion of the proposed study will not only illuminate the role of this disordered
domain in CLK3 (patho)biology, but also provide significant insights into the interplay between the
LCDs and kinase domains in dual specificity kinase functions and dysfunctions.

## Key facts

- **NIH application ID:** 10217666
- **Project number:** 1R03TR003387-01A1
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Priya R. Banerjee
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $158,308
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217666

## Citation

> US National Institutes of Health, RePORTER application 10217666, Deciphering the role of low complexity domains in dual specificity kinase function (1R03TR003387-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10217666. Licensed CC0.

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