Central role of <scp>PI</scp>3K–<scp>SYK</scp> interaction in fibrinogen‐induced lamellipodia and filopodia formation in platelets

Singh, Reeta

doi:10.1002/2211-5463.12149

Cited by 6 publications

(5 citation statements)

References 62 publications

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“…The importance of crosstalk between SYK and PI3K-Akt-mTOR signaling is further supported by the observation that inhibition of PI3K-Akt-mTOR pathway activity enhances the effects of SYK inhibition on AML cell differentiation and viability [112,113]. Subsequent to an activation of the receptor complex Src, an active Src phosphorylates SYK at tyrosine residues, leading to its activation [114]. While active, SYK phosphorylates p110/p85 subunits of PI3K, and hence increasing its catalytic activity, which converts PIP2 to PIP3 [114].…”

Section: Crosstalk Between Pi3k-akt-mtor Pathway and Other Signaling mentioning

confidence: 95%

“…Subsequent to an activation of the receptor complex Src, an active Src phosphorylates SYK at tyrosine residues, leading to its activation [114]. While active, SYK phosphorylates p110/p85 subunits of PI3K, and hence increasing its catalytic activity, which converts PIP2 to PIP3 [114]. Chemical inhibition of SYK has been tested in multiple cells lines and results in a dose-dependent inhibition of mTOR [109].…”

Section: Crosstalk Between Pi3k-akt-mtor Pathway and Other Signaling mentioning

confidence: 99%

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The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells

Nepstad

Hatfield

Grønningsæter

et al. 2020

IJMS

217

150

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Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by uncontrolled proliferation of hematopoietic stem cells in the bone marrow. Malignant cell growth is characterized by disruption of normal intracellular signaling, caused by mutations or aberrant external signaling. The phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway (PI3K-Akt-mTOR pathway) is among one of the intracellular pathways aberrantly upregulated in cancers including AML. Activation of this pathway seems important in leukemogenesis, and given the central role of this pathway in metabolism, the bioenergetics of AML cells may depend on downstream signaling within this pathway. Furthermore, observations suggest that constitutive activation of the PI3K-Akt-mTOR pathway differs between patients, and that increased activity within this pathway is an adverse prognostic parameter in AML. Pharmacological targeting of the PI3K-Akt-mTOR pathway with specific inhibitors results in suppression of leukemic cell growth. However, AML patients seem to differ regarding their susceptibility to various small-molecule inhibitors, reflecting biological heterogeneity in the intracellular signaling status. These findings should be further investigated in both preclinical and clinical settings, along with the potential use of this pathway as a prognostic biomarker, both in patients receiving intensive curative AML treatment and in elderly/unfit receiving AML-stabilizing treatment.

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Section: Crosstalk Between Pi3k-akt-mtor Pathway and Other Signaling mentioning

confidence: 95%

Section: Crosstalk Between Pi3k-akt-mtor Pathway and Other Signaling mentioning

confidence: 99%

The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells

Nepstad

Hatfield

Grønningsæter

et al. 2020

IJMS

217

150

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“…SYK was analyzed due to its involvement in integrin signaling and the formation of WAVE and WASP complexes [ 13 , 14 ]. An amount of 67 samples (81%) showed overexpression with a significant ( p = 0.049) increase from 75% of samples for T1 + T2 to 93% for T3 + T4.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Genes Related to Invadopodia Formation and CTTN in Oral Squamous Cell Carcinoma—A Systematic Gene Expression Analysis

Desel,

Jung,

Purcz

et al. 2023

CIMB

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Successful treatment for any type of carcinoma largely depends on understanding the patterns of invasion and migration. For oral squamous cell carcinoma (OSCC), these processes are not entirely understood as of now. Invadopodia and podosomes, called invadosomes, play an important role in cancer cell invasion and migration. Previous research has established that cortactin (CTTN) is a major inducer of invadosome formation. However, less is known about the expression patterns of CTTN and other genes related to it or invadopodia formation in OSCC during tumor progression in particular. In this study, gene expression patterns of CTTN and various genes (n = 36) associated with invadopodia formation were analyzed to reveal relevant expression patterns and give a comprehensive overview of them. The genes were analyzed from a whole genome dataset of 83 OSCC samples relating to tumor size, grading, lymph node status, and UICC (Union for Internatioanl Cancer Control). The data revealed significant overexpression of 18 genes, most notably CTTN, SRC (SRC proto-onocogene, non-receptor tyrosine kinase), EGFR (epidermal growth factor receptor), SYK (spleen associated tyrosine kinase), WASL (WASP like actin nucleation promotion factor), and ARPC2 (arrestin beta 1) due to their significant correlation with further tumor parameters. This study is one of the first to summarize the expression patterns of CTTN and related genes in a complex group of OSCC samples.

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“…Syk has been shown to activate the PI3K/AKT/mTOR pathway. Active Syk increases the catalytic activity of PI3K, resulting in the conversion of PIP2 to phosphatidylinositol-3,4,5-triphosphate (PIP3) [ 288 ]. This then recruits phosphatidylinositol-dependent kinase 1 (PDK1) and AKT to the cell membrane [ 289 ].…”

Section: Proinflammatory Signaling Pathways Impacted By Trafficked Re...mentioning

confidence: 99%

Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4+ T Cells—Implications for the Pathogenesis of Systemic Lupus Erythematosus

Park

Perl

2023

IJMS

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Endocytic recycling regulates the cell surface receptor composition of the plasma membrane. The surface expression levels of the T cell receptor (TCR), in concert with signal transducing co-receptors, regulate T cell responses, such as proliferation, differentiation, and cytokine production. Altered TCR expression contributes to pro-inflammatory skewing, which is a hallmark of autoimmune diseases, such as systemic lupus erythematosus (SLE), defined by a reduced function of regulatory T cells (Tregs) and the expansion of CD4+ helper T (Th) cells. The ensuing secretion of inflammatory cytokines, such as interferon-γ and interleukin (IL)-4, IL-17, IL-21, and IL-23, trigger autoantibody production and tissue infiltration by cells of the adaptive and innate immune system that induce organ damage. Endocytic recycling influences immunological synapse formation by CD4+ T lymphocytes, signal transduction from crosslinked surface receptors through recruitment of adaptor molecules, intracellular traffic of organelles, and the generation of metabolites to support growth, cytokine production, and epigenetic control of DNA replication and gene expression in the cell nucleus. This review will delineate checkpoints of endosome traffic that can be targeted for therapeutic interventions in autoimmune and other disease conditions.

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Central role of PI3K–SYK interaction in fibrinogen‐induced lamellipodia and filopodia formation in platelets

Cited by 6 publications

References 62 publications

The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells

The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells

Analysis of Genes Related to Invadopodia Formation and CTTN in Oral Squamous Cell Carcinoma—A Systematic Gene Expression Analysis

Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4+ T Cells—Implications for the Pathogenesis of Systemic Lupus Erythematosus

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