Insulin regulation of protein phosphorylation in isolated rat liver nuclear envelopes: potential relationship to mRNA metabolism.

Purrello, Francesco; Burnham, Daniel B.; Goldfine, Ira D.

doi:10.1073/pnas.80.5.1189

Cited by 56 publications

(29 citation statements)

References 53 publications

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“…For example, isolated nuclei have been shown to respond directly to insulin, resulting in an increase in RNA synthesis (49), protein phosphorylation (50), and transport of macromolecules (51,52). In addition, microinjection of an insulin receptor complex was found to stimulate S6 phosphorylation in vivo without recycling to the plasma membrane (13).…”

Section: Discussionmentioning

confidence: 99%

Microinjection of a protein-tyrosine-phosphatase inhibits insulin action in Xenopus oocytes.

Cicirelli

Tonks

Diltz

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

139

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A protein-tyrosine-phosphatase (PTPase 1B; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), specific for phosphotyrosyl residues, was microiqjected into Xenopus oocytes. This resulted in a 3-to 5-fold increase in PTPase activity over endogenous levels. The PTPase blocked the insulin-stimulated phosphorylation oftyrosyl residues on endogenous proteins, including a protein having a molecular mass in the same range as the jl subunit of the insulin or insulin-like growth factor I receptor. PTPase 1B also blocked the activation of an S6 peptide kinase-i.e., an enzyme recognizing a peptide having the sequence RRLSSLRA found in a segment of ribosomal protein S6 and known to be activated early in response to inslin. On the other hand, the insulin stimulation of an S6 kinase, detected by using 40S ribosomes as substrate, was unaffected even though PTPase 1B partially prevented the phosphorylation of ribosomal protein S6 in vivo. Mono Q chromatography of insulin-treated oocyte extracts revealed two main peaks of S6 kinase activity. Fractions from the first peak displayed S6 peptide kinase activity that was essentially abolished in profiles from PTPase lB-injected oocytes. Material from the second peak, which was best revealed by using 40S ribosomes as substrate and had comparatively little S6 peptide kinse activity, was minimally affected by PTPase 1B. These observations suggest that at least two distinct "S6 kinases" are involved in ribosomal protein S6 phosphorylation in vivo and that the activation pathways for these enzymes differ in their sensitivity to PTPase 1B.Since the finding that insulin can induce meiotic cell division in Xenopus oocytes (1, 2), several additional responses to the hormone have been observed. These fall into two categories. One set of responses occurs after stimulation of oocytes with either progesterone or insulin and includes increases in internal pH (3, 4), protein synthesis (5, 6), protein kinase activities (7,8), and protein phosphorylation (3, 9, 10). These changes occur typically 4-6 hr after insulin addition-i.e., just before germinal vesicle breakdown. In contrast, other responses are observed much sooner after hormone addition (<1 hr) and are specific for insulin. These include early increases in S6 peptide kinase (11) and ribosomal protein S6 kinase activities measured in vitro (7) as well as phosphorylation of S6 protein in vivo (7) and an increase in glucose uptake (12). Studies involving the microinjection of the insulin receptor p subunit (13) and antibodies to the insulin receptor (14) into oocytes support the notion that the early and late events are both dependent on tyrosine phosphorylation by the insulin receptor. In other systems, studies involving mutagenesis of the receptor (15-19) and insulinomimetic or inhibitory antibodies (20, 21) also suggest that insulin-stimulated events depend on the activation of the receptor kinase. On the other hand, there are indications that this kinase activity may not be required for all insulin-induced events (22)(23)(2...

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Section: Discussionmentioning

confidence: 99%

Microinjection of a protein-tyrosine-phosphatase inhibits insulin action in Xenopus oocytes.

Cicirelli

Tonks

Diltz

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

139

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“…However, there is indirect and circumstantial evidence for such a role: (1) plant hormones, whose action is believed to be mediated by Ca 2 *, have been shown to regulate gene expression; 341 -342 - 348 (2) the active form of phytochrome (P /r ), which regulates the expression of a number of genes, can modulate Ca 2 * fluxes in plant cells and organdies;"' (in addition, evidence has been presented by Roux's group for a role of Ca 2 * and calmodulin in phytochrome regulated physiological processes 350 ); and (3) a causal link between the phosphorylation of proteins and the regulation of gene expression has been implicated. 351 Furthermore, phosphorylation of proteins is regulated by Ca 2 *-dependent protein kinases (e.g., Ca 2 *-CaM-dependent protein kinases and protein kinase C). For a better understanding of the molecular mechanisms by which Ca 2 * acts, it is essential that the possible role of Ca 2 * in gene regulation be studied.…”

Section: Calcium and Gene Expressionmentioning

confidence: 99%

Calcium messenger system in plants

1987

Critical Reviews in Plant Sciences

331

172

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“…Several laboratories have demonstrated that extracellular insulin affects nuclear processes including mRNA efflux (1), protooncogene expression (2), transcription of tyrosine aminotransferase (3) and phosphoenolpyruvate carboxykinase (4) genes, cell growth (5), and phosphate incorporation into the nuclear envelope (6) and nuclear lamins (7). The first step leading to these effects is the binding of insulin to receptors in the plasma membrane.…”

mentioning

confidence: 99%

Immunological demonstration of the accumulation of insulin, but not insulin receptors, in nuclei of insulin-treated cells.

Soler

Thompson

Smith

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Although insulin is known to regulate nuclear-related processes, such as cell growth and gene transcription, the mechanisms involved are poorly understood. Previous studies suggested that translocation of insulin or its receptor to cell nuclei might be involved in some of these processes. The present investigation demonstrated that intact insulin, but not the insulin receptor, accumulated in nuclei of insulin-treated cells. Cell fractionation studies demonstrated that the nuclear accumulation of 12'I-labeled insulin was time-, temperature-, and insulin-concentration-dependent. Electron microscopic immunocytochemistry demonstrated that the insulin that accumulated in the nucleus was immunologically intact and associated with the heterochromatin. Only 1% of the '25I-labeled insulin extracted from isolated nuclei was eluted from a Sephadex G-50 column as 125I-labeled tyrosine. Plasma membrane insulin receptors were not detected in the nucleus by immuno electron microscopy or when wheat germ agglutininpurified extracts of the nuclei were subjected to PAGE, electrotransfer, and immunoblotting with anti-insulin receptor antibodies. These results suggested that internalized insulin dissociated from its receptor and accumulated in the nucleus without its membrane receptor. We propose that some of insulin's effects on nuclear function may be caused by the translocation of the intact and biologically active hormone to the nucleus and its binding to nuclear components in the heterochromatin.Several laboratories have demonstrated that extracellular insulin affects nuclear processes including mRNA efflux (1), protooncogene expression (2), transcription of tyrosine aminotransferase (3) and phosphoenolpyruvate carboxykinase (4) genes, cell growth (5), and phosphate incorporation into the nuclear envelope (6) and nuclear lamins (7). The first step leading to these effects is the binding of insulin to receptors in the plasma membrane. The remaining events are not understood. In particular, it is not known whether insulin binding to receptors generates signals leading to these nuclear-related events or whether insulin is internalized and interacts directly with components of the nucleus. Miller showed (8) that microinjection of insulin into the cytoplasm of Xenopus laevis oocytes increased RNA and protein synthesis. Also, insulin added to isolated nuclei of oocytes stimulated RNA synthesis, suggesting a direct biological effect of insulin on nuclear function.Although some earlier studies reported that insulin could bind to isolated nuclei (9-11) or accumulate in nuclei of intact IM-9 lymphocytes (12) and rat hepatocytes (13), other studies (14, 15) questioned those findings. This laboratory has provided (16) evidence that receptor-mediated internalization of insulin resulted in a time-and temperature-dependent nuclear accumulation of 1251-labeled insulin and ferritin-labeled insulin in 3T3-L1 adipocytes. The ferritin-labeled insulin was associated with the heterochromatin near nuclear pores. The presence of both 125I and ...

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Insulin regulation of protein phosphorylation in isolated rat liver nuclear envelopes: potential relationship to mRNA metabolism.

Cited by 56 publications

References 53 publications

Microinjection of a protein-tyrosine-phosphatase inhibits insulin action in Xenopus oocytes.

Microinjection of a protein-tyrosine-phosphatase inhibits insulin action in Xenopus oocytes.

Calcium messenger system in plants

Immunological demonstration of the accumulation of insulin, but not insulin receptors, in nuclei of insulin-treated cells.

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