# TYROSINE PHOSPHORYLATION AND CONTROL OF CELL GROWTH

> **NIH NIH R01** · ROGER WILLIAMS HOSPITAL · 1992 · $213,216

## Abstract

Protein-tyrosine kinases have been broadly implicated in the control of
both normal and neoplastic cell proliferation.  Recently, the aberrant bcr-
abl tyrosine kinase, a hallmark of chronic myelogenous leukemia, has been
shown to cause a similar disease in transgenic mice.  Our continuing work
towards understanding the mechanisms whereby tyrosine phosphorylation
regulates cell growth in general, and its role in chronic myelogenous
leukemia in particular, has led us to focus attention on two cellular
proteins which are excellent candidates for physiologically relevant
substrates of tyrosine kinases:  i) a 56-kDa protein constitutively
tyrosine phosphorylated in all CML cells, but tyrosine phosphorylated in
normal cells only in response to certain growth factors (e.g. EGF and CSF-
1):  Using my 1G2-antibody to phosphotyrosine, we have already succeeded in
purifying sufficient quantities of the 56-Da protein to develop anti-
protein monoclonal antibodies, ii) a 62-kDa protein which physically
associates with physiologically important proteins (e.g. GAP, abl,
PLCgamma) containing regions homologous to the second (SH2) domain of src.
Phorbol ester-induced terminal differentiation of CML-cell lines causes a
physical association of the tyrosine-phosphorylated p62 protein with
tyrosine phosphorylated rasGAP (the ras, GTPase-activating protein).  This
is associated with an increase in ras protein activity that appears to be
necessary for the phorbol ester-induced differentiation.

The proposed studies seek to further explore the biochemical and
mechanistic roles of the p56 and p62 proteins in cell proliferation and
differentiation.  Specifically, we seek:  i) to characterize the
biochemical and cellular functions of these proteins; ii) to determine
whether these proteins are structurally homologous to proteins with known
functions; iii) to determine the effects of overexpressing normal and
mutant p56 and p62 proteins in normal fibroblasts, growth-factor dependent
hematopoietic cells, and in CML cells.

## Key facts

- **NIH application ID:** 3178038
- **Project number:** 2R01CA039235-07A1
- **Recipient organization:** ROGER WILLIAMS HOSPITAL
- **Principal Investigator:** RAYMOND A FRACKELTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $213,216
- **Award type:** 2
- **Project period:** 1992-03-06 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178038

## Citation

> US National Institutes of Health, RePORTER application 3178038, TYROSINE PHOSPHORYLATION AND CONTROL OF CELL GROWTH (2R01CA039235-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178038. Licensed CC0.

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