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Prenylation of oncogenic human PTP(CAAX) protein tyrosine phosphatases
C A Cates1, R L Michael, K R Stayrook
1Department of Biology, Indiana University-Purdue University at Indianapolis, 46202, USA.
Abstract:
Many isoprenylated proteins are known to participate in signal transduction, but not all have been identified. Using an in vitro prenylation screen, two human cDNAs (PTP(CAAXI) and PTP(CAAX2)) homologous to the rat PRL-1 and human OV-1 protein tyrosine phosphatase genes were identified. PTP(CAAXI) and PTP(CAAX2) were farnesylated in vitro by mammalian farnesyl:protein transferase, and epitope-tagged PTP(CAAX2) was prenylated in epithelial cells. Overexpression of PTP(CAAXI) and PTP(CAAX2) in epithelial cells caused a transformed phenotype in culture and tumor growth in nude mice. Thus, PTP(CAAXI) and PTP(CAAX2) represent a novel class of isoprenylated, oncogenic protein tyrosine phosphatases.
Insights
Two novel protein tyrosine phosphatases, PTP(CAAXI) and PTP(CAAX2), were identified as isoprenylated and oncogenic. Their overexpression in cells induced a transformed phenotype and tumor growth, highlighting a new class of cancer-promoting enzymes.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Isoprenylated proteins play crucial roles in cellular signaling pathways.
- The full spectrum of isoprenylated proteins and their functions remains incompletely understood.
- Protein tyrosine phosphatases (PTPs) are key regulators of signal transduction.
Purpose of the Study:
- To identify novel isoprenylated proteins involved in cellular signaling.
- To characterize the function and oncogenic potential of newly identified PTPs.
Main Methods:
- In vitro prenylation screening of human cDNAs.
- Biochemical assays using mammalian farnesyl:protein transferase.
- Cellular studies involving overexpression of identified genes in epithelial cells.
- Tumorigenicity assays in nude mice.
Main Results:
- Two human cDNAs, PTP(CAAXI) and PTP(CAAX2), homologous to known PTP genes, were identified.
- Both PTP(CAAXI) and PTP(CAAX2) were confirmed to be farnesylated in vitro and prenylated in vivo.
- Overexpression of PTP(CAAXI) and PTP(CAAX2) led to cellular transformation and tumor formation in vivo.
- These findings establish PTP(CAAXI) and PTP(CAAX2) as a novel class of oncogenic PTPs.
Conclusions:
- PTP(CAAXI) and PTP(CAAX2) are novel, isoprenylated protein tyrosine phosphatases.
- These enzymes possess oncogenic properties, contributing to cellular transformation and tumor growth.
- The discovery expands the known repertoire of signaling proteins involved in cancer development.