Interaction of Wild Type and Dominant-Negative p55PIK Regulatory Subunit of Phosphatidylinositol 3-Kinase with Insulin-Like Growth Factor-1 Signaling Proteins

Mothe, Isabelle; Delahaye, Laurent; Filloux, Chantal; Pons, Sebastián; White, Morris F.; Obberghen, Emmanuel Van

doi:10.1210/mend.11.13.0029

Cited by 13 publications

(7 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenomenon suggests that p55γ may mediate insulin signaling mainly via association with IR rather than IRS‐1. In addition, a recent study demonstrated a tight association between insulin‐like growth factor receptor and p55γ [24], also suggesting a crucial role for p55γ as an adapter protein for insulin or the IGF receptor, rather than IRS‐1 protein.…”

Section: Resultsmentioning

confidence: 97%

Five isoforms of the phosphatidylinositol 3‐kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations

et al. 2001

View full text Add to dashboard Cite

There are five isoforms of the regulatory subunit for the heterodimeric type of phosphatidylinositol 3-kinase. These five regulatory subunit isoforms were overexpressed using an adenovirus transfection system, and their own tyrosine phosphorylations and associations with various tyrosine kinase receptors were investigated. When overexpressed in CHO-PDGFR cells, the associations of these regulatory subunit isoforms with the platelet-derived growth factor receptor were similar. However, when overexpressed in CHO-IR cells, p55gamma exhibited a significantly lower ability to bind with IRS-1 upon insulin stimulation, as compared with other regulatory subunit isoforms. Furthermore, p55alpha and p55gamma were found to be tyrosine-phosphorylated. Finally, interestingly, when overexpressed in CHO-EGFR cells or A431 cells and stimulated with epidermal growth factor (EGF), phosphorylated EGF receptor was detected in p85alpha, p85beta and p50alpha immunoprecipitates, but not in p55alpha and p55gamma immunoprecipitates. In addition, EGF-induced tyrosine phosphorylation was observed in p85alpha, p85beta, p55alpha and p55gamma, but not in p50alpha, immunoprecipitates. Thus, each regulatory subunit exhibits specific responses regarding both the association with tyrosine-phosphorylated substrates and its own tyrosine phosphorylation. These results suggest that each isoform possesses specific roles in signal transduction, based on its individual tyrosine kinase receptor.

show abstract

Section: Resultsmentioning

confidence: 97%

Five isoforms of the phosphatidylinositol 3‐kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations

et al. 2001

View full text Add to dashboard Cite

show abstract

“…The effects of wortmannin on insulin-stimulated glucose transport can be overcome by addition of membrane-permeable forms of PIP $ [46], providing further evidence that PI 3-kinase is involved. Specific evidence for the involvement of class 1a PI 3-kinases in this process was provided by studies with dominant negative forms of the p85 and p55 PIK adapter\regulatory subunits which block insulin stimulation of glucose transport and glucose-transporter translocation [39,266,267]. This has since been bolstered by the finding that constitutively active forms of p110 are able to induce GLUT4 translocation to the plasma membrane in a range of cell types, albeit to a lesser extent than insulin [43,268,269].…”

Section: Vesicle Traffic and Glucose-transporter Translocationmentioning

confidence: 99%

Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling

Shepherd

Withers

Siddle

1998

Biochemical Journal

905

741

View full text Add to dashboard Cite

Insulin plays a key role in regulating a wide range of cellular processes. However, until recently little was known about the signalling pathways that are involved in linking the insulin receptor with downstream responses. It is now apparent that the activation of class 1a phosphoinositide 3-kinase (PI 3-kinase) is necessary and in some cases sufficient to elicit many of insulin's effects on glucose and lipid metabolism. The lipid products of PI 3-kinase act as both membrane anchors and allosteric regulators, serving to localize and activate downstream enzymes and their protein substrates. One of the major ways these lipid products of PI 3-kinase act in insulin signalling is by binding to pleckstrin homology (PH) domains of phosphoinositide-dependent protein kinase (PDK) and protein kinase B (PKB) and in the process regulating the phosphorylation of PKB by PDK. Using mechanisms such as this, PI 3-kinase is able to act as a molecular switch to regulate the activity of serine/threonine-specific kinase cascades important in mediating insulin's effects on endpoint responses.

show abstract

“…Mutation of class III PI 3-kinase, which produces only PI(3)P, impairs vesicular morphology and the endocytic pathway (1,19). Studies using a dominant-negative form of class I PI 3-kinase have implicated PI(3,4)P 2 and/or PI(3,4,5)P 3 in DNA synthesis (20), membrane ruffling (21), and glucose metabolism (22)(23)(24)(25).…”

mentioning

confidence: 99%

Regulation of Phosphoinositide Metabolism, Akt Phosphorylation, and Glucose Transport by PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10) in 3T3-L1 Adipocytes

Ono

Katagiri

Funaki

et al. 2001

Molecular Endocrinology

View full text Add to dashboard Cite

To investigate the roles of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the regulation of 3-position phosphorylated phosphoinositide metabolism as well as insulin-induced Akt phosphorylation and glucose metabolism, wild-type PTEN and its phosphatase-dead mutant (C124S) with or without an N-terminal myristoylation tag were overexpressed in Sf-9 cells and 3T3-L1 adipocytes using baculovirus and adenovirus systems, respectively. When expressed in Sf-9 cells together with the p110alpha catalytic subunit of phosphoinositide 3-kinase, myristoylated PTEN markedly reduced the accumulations of both phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate induced by p110alpha. In contrast, overexpression of the C124S mutants apparently increased these accumulations. In 3T3-L1 adipocytes, insulin-induced accumulations of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate were markedly suppressed by overexpression of wild-type PTEN with the N-terminal myristoylation tag, but not by that without the tag. On the contrary, the C124S mutants of PTEN enhanced insulin-induced accumulations of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Interestingly, the phosphorylation level of Akt at Thr308 (Akt2 at Thr309), but not at Ser473 (Akt2 at Ser474), was revealed to correlate well with the accumulation of phosphatidylinositol 3,4,5-trisphosphate modified by overexpression of these PTEN proteins. Finally, insulin-induced increases in glucose transport activity were significantly inhibited by the overexpression of myristoylated wild-type PTEN, but were not enhanced by expression of the C124S mutant of PTEN. Therefore, in conclusion, 1) PTEN dephosphorylates both phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate in vivo, and the C124S mutants interrupt endogenous PTEN activity in a dominant-negative manner. 2) The membrane targeting process of PTEN may be important for exerting its function. 3) Phosphorylations of Thr309 and Ser474 of Akt2 are regulated differently, and the former is regulated very sensitively by the function of PTEN. 4) The phosphorylation level of Ser474, but not that of Thr309, in Akt2 correlates well with insulin-stimulated glucose transport activity in 3T3-L1 adipocytes. 5) The activity of endogenous PTEN may not play a major role in the regulation of glucose transport activity in 3T3-L1 adipocytes.

show abstract

Interaction of Wild Type and Dominant-Negative p55PIK Regulatory Subunit of Phosphatidylinositol 3-Kinase with Insulin-Like Growth Factor-1 Signaling Proteins

Abstract: In a first series of experiments done in the yeastPIK interacts with key elements in the IGF-I signaling pathway, and that these interactions are negatively modulated by PI 3-kinase itself, providing circuitry for regulatory feedback

Cited by 13 publications

References 44 publications

Five isoforms of the phosphatidylinositol 3‐kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations

Five isoforms of the phosphatidylinositol 3‐kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations

Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling

Regulation of Phosphoinositide Metabolism, Akt Phosphorylation, and Glucose Transport by PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10) in 3T3-L1 Adipocytes

Contact Info

Product

Resources

About