# TYROSINE PROTEIN KINASES AND LYMPHOCYTE ACTIVATION

> **NIH NIH R01** · PURDUE UNIVERSITY · 1987 · $117,302

## Abstract

The association of protein-tyrosine kinase activity with growth factor
receptors and oncogene products suggests an important role for these
enzymes in the regulation of cellular proliferation.  We feel that useful
model systems are needed for studying protein-tyrosine kinases that are
under normal cellular control.  The system we have chosen is lymphocytes,
whose normal response to external stimuli is to proliferate and
differentiate.  It is our hypothesis that protein-tyrosine kinases play
important roles in the regulation of these responses.  To test this
hypothesis we have taken both biochemical and cellular approaches.  Our
biochemical approach has included the identification of a novel 40,000
dalton, cytosolic, protein-tyrosine kinase.  This enzyme appears to be
detectable in lymphoctye homogenates only after the removal of an
endogenous inhibitor.  We have purified this enzyme to near homogeneity
from calf thymus using a number of chromatographic procedures.  We are
proposing to study its physical properties, substrate specificity,
distribution, regulation and role in lymphocyte function.  We have also
identified a T cell-specific, membrane-associated, protein-tyrosine kinase
that is down-regulated in response to mitogens or tumor-promoting phorbol
esters.  We have proposed, in this study, to elucidate the mechanisms that
trigger the loss of this kinase from the membrane and examine the
consequences of this event on its activity and location within the cell.
To determine if the down-regulation of a membrane-associated
protein-tyrosine kinase is a general mechanism of lymphocyte activation, we
have proposed also to examine the effects of mitogens on B lymphocyte
enzymes.  We are also interested in how the various protein-tyrosine
kinases in lymphocytes interact with one another and with other protein
kinases present in the cell.  The methodologies that we propose to use
include:  1) enzyme purification and characterization, 2) ATP:peptide
phosphotransferase assays, 3) cell culture of lymphocyte subpopulations and
transformed lymphoid cell lines, 4) subcellular fractionation and detection
of endogenous protein kinases, 5) antibody production, and 6) biosynthetic
labeling of protein kinases.  It is our contention that a greater
understanding of the biochemical pathways that regulate normal cell growth
and development is necessary to begin to define the lesions within this
pathway that can lead to malignant growth.

## Key facts

- **NIH application ID:** 3175215
- **Project number:** 2R01CA037372-04
- **Recipient organization:** PURDUE UNIVERSITY
- **SAM.gov UEI:** YRXVL4JYCEF5
- **Principal Investigator:** ROBERT L GEAHLEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $117,302
- **Award type:** 2
- **Project period:** 1984-03-15 → 1992-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175215

## Citation

> US National Institutes of Health, RePORTER application 3175215, TYROSINE PROTEIN KINASES AND LYMPHOCYTE ACTIVATION (2R01CA037372-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175215. Licensed CC0.

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