scholarly journals Glycine-extended gastrin activates two independent tyrosine-kinases in upstream of p85/p110 phosphatidylinositol 3-kinase in human colonic tumour cells

2006 ◽  
Vol 12 (12) ◽  
pp. 1859 ◽  
Author(s):  
Audrey Ferrand
Keyword(s):  
Tyrosine Kinases ◽  
Tumour Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Colonic Tumour ◽  
Phosphatidylinositol 3

scholarly journals Highly Prevalent Genetic Alterations in Receptor Tyrosine Kinases and Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase Pathways in Anaplastic and Follicular Thyroid Cancers

2008 ◽  
Vol 93 (8) ◽  
pp. 3106-3116 ◽  
Author(s):  
Zhi Liu ◽  
Peng Hou ◽  
Meiju Ji ◽  
Haixia Guan ◽  
Kimberly Studeman ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinases ◽  
Genetic Basis ◽  
Receptor Tyrosine Kinases ◽  
Genetic Alterations ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Thyroid Cancers ◽  
Mapk Pathways ◽  
Phosphatidylinositol 3

Abstract Context: Genetic alterations in receptor tyrosine kinases (RTKs) and phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK pathways have not been fully defined in anaplastic and follicular thyroid cancers [anaplastic thyroid cancer (ATC), follicular thyroid cancer (FTC)]. Objective: The objective of the study was to explore a wide-range genetic basis for the involvement of these pathways in ATC. Design: We examined mutations and copy number gains of a large panel of genes in these pathways and corresponding phosphorylation of ERK (p-ERK) and Akt. Results: We found frequent copy gains of RTK genes, including EGFR, PDGFRα and -β, VEGFR1 and 2, KIT, and MET and in PIK3Ca, PIK3Cb, and PDK1 genes in the PI3K/Akt pathway. Mutations of Ras, PIK3Ca, PTEN, and BRAF genes and RET/PTC rearrangements were common, whereas mutations in PDK1, Akt1, Akt2, and RTK genes were uncommon in ATC. Overall, 46 of 48 ATC (95.8%) harbored at least one genetic alteration, and coexistence of two or more was seen in 37 of 48 ATC (77.1%). These genetic alterations were somewhat less common in FTC. Genetic alterations that could activate both the PI3K/Akt and MAPK pathways were found in 39 of 48 ATC (81.3%). RTK gene copy gains were preferentially associated with p-Akt, suggesting their dominant role in activating the PI3K/Akt pathway. The phosphorylation of Akt was far more common than p-ERK in FTC, and both were relatively common and often coexisted in ATC. Conclusions: Genetic alterations in the RTKs and PI3K/Akt and MAPK pathways are extremely prevalent in ATC and FTC, providing a strong genetic basis for an extensive role of these signaling pathways and the development of therapies targeting these pathways for ATC and FTC, particularly the former.

scholarly journals Phosphatidylinositol-3-kinase activity is required for the anti-ig- mediated growth inhibition of a human B-lymphoma cell line

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 202-210 ◽  
Author(s):  
M Beckwith ◽  
RG Fenton ◽  
IM Katona ◽  
DL Longo
Keyword(s):  
Growth Inhibition ◽  
Tyrosine Kinases ◽  
Specific Inhibitor ◽  
Phosphatidylinositol 3 Kinase ◽  
Intact Cells ◽  
B Lymphoma ◽  
Cycle Arrest ◽  
Pi3k Activity ◽  
B Lymphoma Cells ◽  
Phosphatidylinositol 3

Stimulation of B lymphocytes through the Ig receptor initiates a cascade of biochemical changes, which can ultimately lead to either activation and growth, or cell-cycle arrest and cell death. One of the critical events that occurs in both cases is the activation of tyrosine kinases, and the resulting phosphorylation of a variety of proteins on tyrosine residues. In this report we identify one of the substrates of phosphorylation as the 85-kD subunit of the enzyme phosphatidylinositol-3 kinase (PI3K), and show that both anti-IgM and anti-IgD stimulation results in an increase in the anti-phosphotyrosine-precipitable PI3K activity. Furthermore, we show that the potent and specific inhibitor of PI3K, Wortmannin, can completely abrogate anti-Ig-mediated growth inhibition without affecting tyrosine kinase induction or protein kinase C (PKC) activation. Treatment of intact cells with Wortmannin results in an irreversible decrease in anti-Ig-induced PI3K activity, suggesting that the effect of Wortmannin on anti-Ig-mediated growth inhibition is caused by its inactivation of PI3K activity. Taken together, these data show that activation of PI3K is a critical component of the anti-Ig-initiated signaling cascade that leads to growth inhibition of human B lymphoma cells.

scholarly journals Src-family Tyrosine Kinases in Activation of ERK-1 and p85/p110-phosphatidylinositol 3-Kinase by G/CCKBReceptors

1999 ◽  
Vol 274 (29) ◽  
pp. 20657-20663 ◽  
Author(s):  
Laurence Daulhac ◽  
Aline Kowalski-Chauvel ◽  
Lucien Pradayrol ◽  
Nicole Vaysse ◽  
Catherine Seva
Keyword(s):  
Tyrosine Kinases ◽  
Phosphatidylinositol 3 Kinase ◽  
Src Family Tyrosine Kinases ◽  
Phosphatidylinositol 3

scholarly journals Heat Shock Activates c-Src Tyrosine Kinases and Phosphatidylinositol 3-Kinase in NIH3T3 Fibroblasts

1997 ◽  
Vol 272 (49) ◽  
pp. 31196-31202 ◽  
Author(s):  
Richard Z. Lin ◽  
Zhuo-Wei Hu ◽  
Jane H. Chin ◽  
Brian B. Hoffman
Keyword(s):  
Heat Shock ◽  
Tyrosine Kinases ◽  
Phosphatidylinositol 3 Kinase ◽  
Src Tyrosine Kinases ◽  
Phosphatidylinositol 3

scholarly journals Phosphatidylinositol 3-Kinase and Antiestrogen Resistance in Breast Cancer

2011 ◽  
Vol 29 (33) ◽  
pp. 4452-4461 ◽  
Author(s):  
Todd W. Miller ◽  
Justin M. Balko ◽  
Carlos L. Arteaga
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinases ◽  
De Novo ◽  
Clinical Investigation ◽  
Endocrine Resistance ◽  
Pi3k Pathway ◽  
Antiestrogen Resistance ◽  
Phosphatidylinositol 3 Kinase ◽  
Positive Breast Cancer ◽  
Phosphatidylinositol 3

Although antiestrogen therapies targeting estrogen receptor (ER) α signaling prevent disease recurrence in the majority of patients with hormone-dependent breast cancer, a significant fraction of patients exhibit de novo or acquired resistance. Currently, the only accepted mechanism linked with endocrine resistance is amplification or overexpression of the ERBB2 (human epidermal growth factor receptor 2 [HER2]) proto-oncogene. Experimental and clinical evidence suggests that hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway, the most frequently mutated pathway in breast cancer, promotes antiestrogen resistance. PI3K is a major signaling hub downstream of HER2 and other receptor tyrosine kinases. PI3K activates several molecules involved in cell-cycle progression and survival, and in ER-positive breast cancer cells, it promotes estrogen-dependent and -independent ER transcriptional activity. Preclinical tumor models of antiestrogen-resistant breast cancer often remain sensitive to estrogens and PI3K inhibition, suggesting that simultaneous targeting of the PI3K and ER pathways may be most effective. Herein, we review alterations in the PI3K pathway associated with resistance to endocrine therapy, the state of clinical development of PI3K inhibitors, and strategies for the clinical investigation of such drugs in hormone receptor–positive breast cancer.

Thrombin-dependent association of phosphatidylinositol-3 kinase with p60c-src and p59fyn in human platelets

1990 ◽  
Vol 10 (7) ◽  
pp. 3806-3809
Author(s):  
J S Gutkind ◽  
P M Lacal ◽  
K C Robbins
Keyword(s):  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Human Platelets ◽  
Protein Tyrosine Kinases ◽  
Reaction Products ◽  
Phosphatidylinositol 3 Kinase ◽  
Protein Tyrosine ◽  
Nonreceptor Protein Tyrosine Kinases ◽  
Pi Kinase ◽  
Phosphatidylinositol 3

Recent studies have shown that ligand-activated growth factor receptors as well as transforming versions of nonreceptor protein-tyrosine kinases physically associate with phosphatidylinositol-3 kinase (PI-3 kinase). Reasoning that PI-3 kinase might also play a role in the normal functions of nonreceptor kinases, we sought to determine whether association with PI-3 kinase might serve as a measure of nonreceptor protein-tyrosine kinase activation under physiological conditions. We found that p60c-src as well as p59fyn, the product of another member of the src family of proto-oncogenes, physically associated with a PI kinase activity within 5 s after exposure to thrombin. Furthermore, PI kinase reaction products generated in p60v-src, p60c-src or p59fyn containing immunoprecipitates were indistinguishable, demonstrating the identity of the associated enzyme as PI-3 kinase. These findings demonstrate a thrombin-dependent interaction between p60c-src or p59fyn and PI-3 kinase and suggest a role for nonreceptor protein-tyrosine kinases in human platelet signal transduction.

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