Multiple roles for the p85α isoform in the regulation and function of PI3K signalling and receptor trafficking

Mellor, Paul; Furber, Levi A.; Nyarko, Jennifer N.K.; Anderson, Deborah H.

doi:10.1042/bj20111164

Cited by 80 publications

(87 citation statements)

References 211 publications

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“…Although Miller et al [26] also failed to find any differences in lung cancer, they did find higher CRK expression at more advanced clinical stages. CRK is known to interact with the p85α subunit and lead to PI3K signaling pathway activation [25], which may account for the strong positive correlation observed in the present study between CRK mRNA and FZD4 or CXCR4, and the medium correlation with PIK3R1. What is more, CRK mediates small G-protein interactions, and both CXCR4 and FZD4 are members of the GPCR family [5].…”

Section: Discussionsupporting

confidence: 67%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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Abstract. BACKGROUND:Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers -and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS:We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.

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Section: Discussionsupporting

confidence: 67%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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“…SARA localizes to early endosomal subcellular compartments (4) (5), and inhibition of PI3K may impact endocytosis (9). We therefore assessed whether inhibiting PI3K resulted in mislocalization of SARA away from endosomes leading to its degradation.…”

Section: Resultsmentioning

confidence: 99%

“…The p85 isoforms are a group of related proteins encoded by the Pik3r1 (p85␣, p55␣, p50␣), Pik3r2 (p85␤), and Pik3r3 (p55␥) genes. The most abundant and well characterized regulatory subunit, p85␣, contains the domains within the smaller isoforms but also has an N-terminal SH3 domain and a GTPase-activating protein (GAP) domain (also called a BCR homology domain), as well as two proline-rich regions, to provide added binding functions and regulatory capacities (9). In quiescent cells, the p85-p110 complex is cytosolic, and p110-encoded PI3K activity is repressed.…”

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confidence: 99%

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Phosphatidylinositol 3-Kinase and Rab5 GTPase Inversely Regulate the Smad Anchor for Receptor Activation (SARA) Protein Independently of Transforming Growth Factor-β1

Runyan

Liu

Schnaper

2012

Journal of Biological Chemistry

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Background: SARA promotes an epithelial cell phenotype, whereas its down-regulation is permissive for EMT. Results: PI3K inhibition decreases SARA protein expression, likely through alterations in Rab5-containing endosomes. Conclusion: PI3K signaling supports an epithelial phenotype. Significance: PI3K has complex effects in fibrogenesis. Our data suggest an antifibrotic action of PI3K that involves maintaining SARA expression.

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“…p85α selects binding proteins and regulates phosphorylation. 19 It binds to activated (phosphorylated) protein tyrosine kinases (Tyr kinases), through its SH2 domain, and acts as an adaptor, mediating the association of the p110 catalytic unit to the plasma membrane. It is required for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues.…”

Section: Pik3r1 Genementioning

confidence: 99%

Phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as therapeutic targets in breast cancer

Dirican

Akkiprik

2017

Tumour Biol.

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Breast cancer is the most commonly diagnosed cancer among women in Turkey and worldwide. It is considered a heterogeneous disease and has different subtypes. Moreover, breast cancer has different molecular characteristics, behaviors, and responses to treatment. Advances in the understanding of the molecular mechanisms implicated in breast cancer progression have led to the identification of many potential therapeutic gene targets, such as Breast Cancer 1/2, phosphatidylinositol 3-kinase catalytic subunit alpha, and tumor protein 53. The aim of this review is to summarize the roles of phosphatidylinositol 3-kinase regulatory subunit 1 (alpha) (alias p85α) and phosphatase and tensin homolog in breast cancer progression and the molecular mechanisms involved. Phosphatase and tensin homolog is a tumor suppressor gene and protein. Phosphatase and tensin homolog antagonizes the phosphatidylinositol 3-kinase/ AKT signaling pathway that plays a key role in cell growth, differentiation, and survival. Loss of phosphatase and tensin homolog expression, detected in about 20%-30% of cases, is known to be one of the most common tumor changes leading to phosphatidylinositol 3-kinase pathway activation in breast cancer. Instead, the regulatory subunit p85α is a significant component of the phosphatidylinositol 3-kinase pathway, and it has been proposed that a reduction in p85α protein would lead to decreased negative regulation of phosphatidylinositol 3-kinase and hyperactivation of the phosphatidylinositol 3-kinase pathway. Phosphatidylinositol 3-kinase regulatory subunit 1 protein has also been reported to be a positive regulator of phosphatase and tensin homolog via the stabilization of this protein. A functional genetic alteration of phosphatidylinositol 3-kinase regulatory subunit 1 that results in reduced p85α protein expression and increased insulin receptor substrate 1 binding would lead to enhanced phosphatidylinositol 3-kinase signaling and hence cancer development. Phosphatidylinositol 3-kinase regulatory subunit 1 underexpression was observed in 61.8% of breast cancer samples. Therefore, expression/alternations of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog genes have crucial roles for breast cancer progression. This review will summarize the biological roles of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog in breast cancer, with an emphasis on recent findings and the potential of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as a therapeutic target for breast cancer therapy. KeywordsPhosphatidylinositol 3-kinase regulatory subunit 1, phosphatase and tensin homolog, phosphatidylinositol 3-kinase, breast cancer, therapy, phosphatidylinositol 3-kinase catalytic subunit alpha Date

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Multiple roles for the p85α isoform in the regulation and function of PI3K signalling and receptor trafficking

Cited by 80 publications

References 211 publications

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Phosphatidylinositol 3-Kinase and Rab5 GTPase Inversely Regulate the Smad Anchor for Receptor Activation (SARA) Protein Independently of Transforming Growth Factor-β1

Phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as therapeutic targets in breast cancer

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