Phosphatidylinositol 3-Kinase and Protein Kinase C as Molecular Determinants of Chemoresistance in Breast Cancer

2002 ◽  
Author(s):  
Amanda P. Parker ◽  
Barbara S. Beckman ◽  
Matthew Burow
Keyword(s):  
Breast Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase C ◽  
Molecular Determinants ◽  
Phosphatidylinositol 3

scholarly journals Signalling-competent truncated forms of ErbB2 in breast cancer cells: differential regulation by protein kinase C and phosphatidylinositol 3-kinase

1999 ◽  
Vol 344 (2) ◽  
pp. 339-348 ◽  
Author(s):  
Azucena ESPARÍS-OGANDO ◽  
Elena DÍAZ-RODRÍGUEZ ◽  
Atanasio PANDIELLA
Keyword(s):  
Breast Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Receptor Tyrosine Kinase ◽  
Breast Cancer Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase C ◽  
Phosphatidylinositol 3

Alterations that affect the ectodomain of receptor tyrosine kinases are often associated with constitutive activation of the enzymic activity of the mutant cell-associated receptor. Since the ectodomain of the ErbB2 receptor tyrosine kinase has been detected as a soluble fragment in the culture supernatant of cells and serum from patients with advanced breast cancer, the possible presence of cell-associated truncated forms of ErbB2 in cancer cells was investigated. Several cell-bound N-terminal truncated forms of ErbB2 were identified in breast cancer cells overexpressing this receptor. The presence of the truncated fragments was independent of lysosomal/proteasomal activity, indicating that classical receptor tyrosine kinase degradation systems were not involved in the N-terminal cleavages. The presence of these truncated forms of ErbB2 was up-regulated by protein kinase C and neuregulin; and down-regulated by phosphatidylinositol 3-kinase, and monoclonal antibodies that target the ectodomain of ErbB2, indicating that N-terminal cleavages of ErbB2 were regulated by multiple mechanisms. The truncated fragments were tyrosine-phosphorylated under resting conditions, and associated with the signalling intermediates Shc and Grb2. It is therefore likely that these truncated forms may be endowed with constitutive activity that allows them to permanently signal.

scholarly journals Ca2+-Evoked Serotonin Secretion by Parafollicular Cells: Roles in Signal Transduction of Phosphatidylinositol 3′-kinase, and the γ and ζ Isoforms of Protein Kinase C

2000 ◽  
Vol 20 (4) ◽  
pp. 1365-1373 ◽  
Author(s):  
Kuo-peing Liu ◽  
Shu-chi Hsiung ◽  
Mella Adlersberg ◽  
Todd Sacktor ◽  
Michael D. Gershon ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase C ◽  
Parafollicular Cells ◽  
Serotonin Secretion ◽  
Phosphatidylinositol 3

scholarly journals Protein Kinase C-ζ as a Downstream Effector of Phosphatidylinositol 3-Kinase during Insulin Stimulation in Rat Adipocytes

1997 ◽  
Vol 272 (48) ◽  
pp. 30075-30082 ◽  
Author(s):  
Mary L. Standaert ◽  
Lamar Galloway ◽  
Purushotham Karnam ◽  
Gautam Bandyopadhyay ◽  
Jorge Moscat ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Stimulation ◽  
Rat Adipocytes ◽  
Downstream Effector ◽  
Kinase C ◽  
Phosphatidylinositol 3

Leptin Constrains Phospholipase C-Protein Kinase C-Induced Insulin Secretion via a Phosphatidylinositol 3-Kinase-Dependent Pathway

2003 ◽  
Vol 228 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Joo-Won Lee ◽  
Andrew G. Swick ◽  
Dale R. Romsos
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Phosphatidylinositol 3 Kinase ◽  
C Protein ◽  
Kinase C ◽  
Pka Pathway ◽  
Stimulation Of ◽  
Phosphatidylinositol 3

Leptin-deficient Lepob/Lepob mice hypersecrete insulin in response to acetylcholine stimulation of the phospholipase C-protein kinase C (PLC-PKC) pathway, and leptin constrains this hypersecretion. Leptin has been reported to activate phosphatidylinositol 3-kinase (PI 3-K) and subsequently phosphodiesterase (PDE) to impair protein kinase A (PKA)-induced insulin secretion from cultured islets of neonatal rats. We determined if PKA-induced insulin secretion was also hyperresponsive in Islets from Lepob/Lepob mice, and if leptin impaired this pathway in islets from these mice. Additionally, the possible role for PI 3-K and PDE in leptin-induced control of acetylcholine-induced insulin secretion was examined. Stimulation of Insulin secretion with GLP-1, forskolin (an activator of adenylyl cyclase), or IBMX (an inhibitor of PDE) did not cause hypersecretion of insulin from islets of young Lepob/Lepob mice, and leptin did not inhibit GLP-1-induced insulin secretion from islets of these mice. Inhibition of PDE with IBMX also did not block leptin-induced inhibition of acetylcholine-mediated insulin secretion from islets of Lepob/Lepob mice. But, preincubation of islets with wortmannin, an Inhibitor of PI 3-K activity, blocked the ability of leptin to constrain acetylcholine-induced insulin secretion from islets of Lepob/Lepob mice. We conclude that the capacity of the PKA pathway to stimulate insulin secretion is not increased in islets from young Lepob/Lepob mice, and that leptin does not regulate this pathway in islets from mice. Leptin may stimulate PI 3-K to constrain PLC-PKC-induced insulin secretion from Islets of Lepob/Lepob mice.

Protein kinase C modulates negatively the hepatocyte growth factor-induced migration, integrin expression and phosphatidylinositol 3-kinase activation

2004 ◽  
Vol 16 (4) ◽  
pp. 505-513 ◽  
Author(s):  
Annamária Gujdár ◽  
Szabolcs Sipeki ◽  
Erzsébet Bander ◽  
László Buday ◽  
Anna Faragó
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Hepatocyte Growth Factor ◽  
Integrin Expression ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase Activation ◽  
Kinase C ◽  
Hepatocyte Growth ◽  
Phosphatidylinositol 3
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