Transformation of cells overexpressing a tyrosine kinase by phospholipase D1 and D2.
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.
Joseph
T
T
Department of Biological Sciences, Hunter College, New York, New York 10021, USA.
Wooden
R
R
Bryant
A
A
Zhong
M
M
Lu
Z
Z
Foster
D A
DA
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics; D015870:Gene Expression; D016391:Genes, src; D010739:Phospholipase D / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D019061:src-Family Kinases
D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1