# SIGNAL TRANSDUCTION IN CELL PROLIFERATION

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1991 · $183,122

## Abstract

The objective of the proposed research is to determine the extent
to which GTP-binding regulatory proteins (G proteins) participate
in pathways of signal transduction relevant to normal and aberrant
cell proliferation.  A primary focus of this research is the extent
to which G proteins mediate the mitogenic actions of growth
factors:  G proteins that participate in pathways of transduction
utilized by growth factors will be identified, and the regulation
of G proteins serving these and other forms of transduction will
be assessed.  Studies will extend to malignant transformation, a
model of oncogenesis wherein pronounced alterations in second-
messenger systems occur.  The first goal of the proposed research
is to develop monoclonal and peptide-specific antibodies
recognizing the 35-kDa form of the beta subunit and the gamma
subunit(s) common to G proteins; these will complete the array of
immunological tools required for the analysis of G protein
regulation.  A subsequent goal is the definition of G proteins that
exist within cells to be investigated (i.e., mouse 3T3, normal rat
kidney, and rat embryo fibroblasts).  This will be achieved by
employment of immunoadsorption chromatography in conjunction with
various indices of primary structure.  The third goal is the
isolation and definition of G proteins that physically interact
with receptors for platelet-derived growth factor, bombesin,
insulin, epidermal growth factor, and transforming growth factor-
beta.  Receptor/G protein complexes pre-existing within membrane
will be isolated by affinity chromatography under conditions
previously demonstrated to stabilize noncovalent interactions; a
G protein(s) sensitive to Islet-activating protein mediates the
actions of at least bombesin, and this will be identified by
procedures of concomitant (32P)ADP-ribosylation.  A fourth goal
entails assessment of the extent to which G proteins serve as
targets for growth factor-elicited enzymic activities or regulation
of transcription.  Alterations in the quantities of G proteins and
the occurrence of post-translational modifications will be examined
by means of immunotransfer blotting and radiolabeling in
conjunction with electrophoretic procedures. The final goal of this
proposal is the assessment of G protein regulation in relation to
malignant transformation effected by Rous and Kirsten sarcoma
viruses; the obtained results will be integrated with those
previously acquired in this laboratory.  The proposed research
addresses the extent to which G proteins are either engaged or
modified within the context of cell proliferation.  Accordingly,
this research will provide information relevant to the basic
actions of growth factors and the sensitivity of cells to external
stimuli during normal and oncogenic growth.

## Key facts

- **NIH application ID:** 3179071
- **Project number:** 5R01CA039712-07
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** David Randell Manning
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $183,122
- **Award type:** 5
- **Project period:** 1985-04-01 → 1993-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179071

## Citation

> US National Institutes of Health, RePORTER application 3179071, SIGNAL TRANSDUCTION IN CELL PROLIFERATION (5R01CA039712-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179071. Licensed CC0.

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