Abstract
Phospholipase D (PLD) activity is elevated in response to most mitogenic signals. Two mammalian PLD genes (PLD1 and PLD2) have been cloned and their gene products have been characterized. PLD1 is a downstream target of the Ras/RalA GTPase cascade implicated in mitogenic and oncogenic signaling. Consistent with a role in mitogenic signaling, elevated expression of PLD1 transforms cells overexpressing the epidermal growth factor (EGF) receptor (EGFR). However, PLD2 colocalizes with the EGFR in caveolin-enriched light membrane microdomains. We therefore investigated whether PLD2 could also contribute to the transformation of cells overexpressing a tyrosine kinase. We report here that elevated expression of PLD2 transforms rat fibroblasts overexpressing either the EGFR or c-Src. Since overexpression of a tyrosine kinase is a common genetic alteration in several human cancers, these data suggest that elevation of either PLD1 or PLD2 may contribute to the progression to a malignant phenotype in cells with elevated tyrosine kinase activity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1019-1024 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 289 |
| Issue number | 5 |
| DOIs | |
| State | Published - Dec 21 2001 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank M. Frohman (SUNY, Stony Brook) for the hPLD1 and mPLD2 genes used to generate the inducible PLD expression vectors. This investigation was supported by grant CA46677 from the National Cancer Institute, National Institutes of Health (to D.A.F.) and a Research Centers in Minority Institutions (RCMI) Award RR-03037 from the Division of Research Resources, National Institutes of Health (to Hunter College).
