The mechanism involved in the regulation of phospholipase Cgamma1 activity in cell migration.
Activation of the enzyme phospholipase C (PLC) leads to the formation of second messengers inositol 1,4,5-trisphosphate and diacylglycerol. Tyrosine kinase receptors activate this reaction through PLCgamma isoenzymes. PLCgamma activity involves its activation with, and phosphorylation by, receptor tyrosine kinases. Recently, it has been shown that phosphoinositide 3-kinase (PI 3-K) may regulate PLCgamma activity through the interaction of the PI 3-K product phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P(3)) and the PLCgamma pleckstrin homology (PH) domain. In an effort to understand the signalling pathway that involves PI 3-K regulation of PLCgamma, we found that EGF induces a PI 3-K-dependent translocation of PLCgamma1 at the leading edge of migrating cells in a wound healing assay. Similarly, the isolated PH, but not the Src-homology (SH) domains, N-SH2 or SH3, of PLCgamma1, translocates at the leading edge. Our experiments also showed that stable PH PLCgamma1 expression blocks epidermal growth factor (EGF)- and serum-induced cell motility and increases cell adhesion in MDA-MB-231 cells. This may suggest that influence of PI 3-K on PLCgamma1 could be relevant in cell migration, where PLCgamma1 seems to play a key role by modulating a series of events involved in actin polymerization.
Piccolo
Enza
E
Department of Oncology and Neuroscience, Section of Medical Oncology, Universita 'G. D'Annunzio', Via dei Vestini 1, 66100 Chieti, Italy.
Innominato
Pasquale F
PF
Mariggio
Maria A
MA
Maffucci
Tania
T
Iacobelli
Stefano
S
Falasca
Marco
M
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D021381:Protein Transport; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology*; D010738:Type C Phospholipases / Q000378:metabolism*; D018909:src Homology Domains / Q000502:physiology
D007527:Isoenzymes; D008164:Luminescent Proteins; D018129:Phosphatidylinositol Phosphates; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma