# HUMAN T LYMPHOCYTE FUNCTION IN LUPUS ERYTHEMATOSUS

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1990 · $119,669

## Abstract

We have described a disorder of cAMP metabolism in T
lymphocytes of subjects with systemic lupus erythematosus (SLE)
Our recent identification of defective cAMP -dependent
phosphorylation of proteins in intact SLE T lymphocytes suggests
a disorder of cAMP -dependent protein kinase (Protein kinase A)
The objective of this proposal is to identify and characterize the
abnormal protein kinase A function in SLE T lymphocytes by
quantifying cAMP -dependent protein kinase activities and the
amounts of the enzyme's constituent subunits, the types I (RI) and
II (RII) regulatory and catalytic subunits (C subunit).  The specific
aims of this proposal are (a) to compare protein kinase A
activities in the nonparticulate and particulate fractions of T
lymphocytes and T lymphocyte subsets from active and inactive
SLE subjects with controls.  cAMP -dependent protein kinase
activity will be quantified by measuring the phosphorylation of
histone and Kemptide in nonparticulate and particulate T cell
extracts. (b) We will purify partially the cAMP -dependent protein
kinases of SLE T lymphocytes by DEAE -cellulose chromatography
in order to determine the presence of anomalous RI, RII and/or C
subunits.  Anomalous RI or RII subunits can exhibit altered cAMP
binding while anomalous C subunits can possess reduced binding
affinity for ATP.  (c) The amounts of protein kinase A subunits
will be quantified by ELISA and nitrocellulose immunolabeling to
determine whether a deficiency of one or more subunits exists to
explain altered protein kinase activities.  Differences in the
kinase activities and/or amounts of a kinase of a kinase subunit
between T cell subsets will be quantified to determine whether a
restricted kinase defect exists.  Since the T lymphocyte plays an
integral role in both cellular and humoral immunity, it is
important to discover whether a defective cAMP pathway
accounts, in part, for the aberrant immunoregulation in SLE.
Thus, our longterm goal is to determine whether defective protein
kinase A function results in abnormal suppressor cell activity.
The identification of a protein kinase A defect should provide
important insights into the pathogenesis of this autoimmune
disorder.

## Key facts

- **NIH application ID:** 3159575
- **Project number:** 5R01AR039501-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** GARY M KAMMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $119,669
- **Award type:** 5
- **Project period:** 1988-07-01 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159575

## Citation

> US National Institutes of Health, RePORTER application 3159575, HUMAN T LYMPHOCYTE FUNCTION IN LUPUS ERYTHEMATOSUS (5R01AR039501-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159575. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*