# KERATINOCYTE TRANSGLUTAMINASE--STRUCTURE AND REGULATION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 1993 · $158,209

## Abstract

Keratinocyte transglutaminase (TGK) is a membrane-bound phosphoprotein
responsible for cross-linked envelope formation during terminal
differentiation in epidermal cells.  To understand the molecular basis
for TGK expression and function during the differentiation program, this
proposal investigates the posttranslational modifications to which the
enzyme is subject and is transcriptional regulation by effectors in the
steroid superfamily (retinoids, T3, glucocorticoids, TCDD).  First,
features of the amino acid sequence near the amino terminus which
influence membrane anchorage will be explored.  Mutagenesis of the
acylation site, a cluster of 5 Cys residues, will be conducted to
determine the importance of its hydrophobicity and the role of individual
residues.  The minimal TGK sequence capable of inducing anchorage when
fused to a freely soluble protein (involucrin) will be determined and,
on that basis, peptide substrates and inhibitors of fatty acid
transacylase will be designed.  In a second line of investigation, Ser
residues subject to phorbol ester-stimulated phosphorylation will be
identified by (i) using synthetic peptides as protein kinase C substrates
and (ii) examining the phosphorylation of site-directed TGK mutants.
Further, possible interdependence of fatty acid acylation and
phosphorylation will be studied.  In addition, the enzymatic basis will
be examined for a deficiency in TGK phosphorylation exhibited by an
immortalized human epidermal cell line.  The final aspect of the proposal
investigates the molecular basis for regulation of TGK mRNA levels by
retinoids, T3, glucocorticoids and TCDD.  Response elements in the 5'-
flanking DNA that regulate transcription will be identified by luciferase
reporter transfection and by mobility shift experiments.  If warranted,
transcriptional regulation by receptor level modulation and receptor
protein interactions will be explored.  The results of this work will
provide insight not only into the regulation of keratinocyte
differentiation but will also contribute more generally to
characterization of protein fatty acid acyltransferases and of a
potentially important difference in kinase expression among neoplastic
and normal keratinocytes.

## Key facts

- **NIH application ID:** 3155522
- **Project number:** 2R01AR027130-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **SAM.gov UEI:** TX2DAGQPENZ5
- **Principal Investigator:** ROBERT H RICE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $158,209
- **Award type:** 2
- **Project period:** 1989-09-30 → 1995-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155522

## Citation

> US National Institutes of Health, RePORTER application 3155522, KERATINOCYTE TRANSGLUTAMINASE--STRUCTURE AND REGULATION (2R01AR027130-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155522. Licensed CC0.

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