# PROTEIN KINASE ACTIVITY AND HSV-2 TRANSFORMING POTENTIAL

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1993 · $176,724

## Abstract

HSV-2 leads to neoplastic transformation of normal diploid cells.
However, the role that the virus plays in carcinogenesis is unclear and
doubt has been voiced about the very existence of oncogenes.  The
proposed studies are based on the following recent findings from our
laboratory: (i) the large subunit of HSV-2 ribonucleotide reductase
(ICP10) has an associated protein kinase (PK) activity that appears to
be coded by the minimal transforming DNA fragment (mtrIII) and is also
localized in the plasma membrane, (ii) the PK minigene has properties
similar to those of growth factor receptors (GFRs) and (iii) cell DNA
contains mtrIII-homologous sequences.  The working hypothesis is that
HSV-2 mediated hamster cell transformation involves this PK function
which by analogy to retroviral oncogenes has a cellular counterpart and
originated from a truncated, as yet unidentified GFR or a PK in the GF
pathways.  The proposed studies seek to define the role of the PK
function in transformation and assess the contribution of specific
catalytic domains and of the transmembrane helical region.  Deletion
mutants that respectively lack the PK or RR domains were prepared since
the last review. Others, in the non-catalytic region N-terminal to the
PK (includes the transmembrane helix) will be prepared.  Specific PK
catalytic domains considered of functional significance for other PKs,
and the transmembrane helical region will be mutated by site-directed
mutagenesis and expressed in the constitutive expression vector.  All
mutants will be studied for: (i) ICP10 synthesis, (ii) PK activity,
(iii) subcellular localization and (iv) transforming ability.
Transformed lines will be studied for DNA maintenance and gene
expression using Sl nuclease assay.  The potential mechanism of
transformation will be studied.  Hybrid plasmids consisting of the PK
minigene and the extracellular ligand binding domain of the epidermal
growth factor receptor (EGFR) will be constructed and lines will be
established.  They will be studied for synthesis processing and cell
surface localization of the hybrid protein.  Ligand-mediated activation
of the PK minigene will be determined and correlated with
phosphatidylinositol turnover, nuclear oncogene (c-myc, fos, jun)
activation (increased expression) and transforming potential.
Characterization of this novel ICP10-PK and definition of its
involvement in the neoplastic process should help elucidate problems
relating to the mechanism of HSV-2 induced neoplastic transformation.

## Key facts

- **NIH application ID:** 3179021
- **Project number:** 5R01CA039691-06
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** Laure Aurelian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $176,724
- **Award type:** 5
- **Project period:** 1985-12-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179021

## Citation

> US National Institutes of Health, RePORTER application 3179021, PROTEIN KINASE ACTIVITY AND HSV-2 TRANSFORMING POTENTIAL (5R01CA039691-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179021. Licensed CC0.

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