Insulin-modulated transport of RNA from isolated liver nuclei

Schumm, Dorothy E.; Webb, Thomas E.

doi:10.1016/0003-9861(81)90190-9

Cited by 52 publications

(27 citation statements)

References 24 publications

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“…At higher insulin concentrations, the increased enzyme activity decreased toward control levels. This biphasic effect is similar to that seen in other subcellular systems (8,10,11). In ten separate experiments with 10 pM insulin, enzyme 1006 activity was increased by 27.1 + 1.1 percent (mean ± standard error).…”

Section: Insulin Stimulation Of Nucleoside Triphosphatase Activity Insupporting

confidence: 87%

“…Presumably, after insulin is internalized, it is able to interact with intracellular organelles. Finally, the direct addition of insulin to isolated nuclei is reported to increase mRNA transport (8), and the present study demonstrates a direct effect of insulin on the nuclear envelope nucleoside triphosphatase, the enzyme that controls mRNA transport (19). The possibility exists, therefore, that insulin regulates the nuclear envelope to increase mRNA transport either directly or by the generation of a second messenger at the nuclear surface.…”

Section: Insulin Stimulation Of Nucleoside Triphosphatase Activity Inmentioning

confidence: 57%

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Insulin Stimulation of Nucleoside Triphosphatase Activity in Isolated Nuclear Envelopes

Vigneri

Clawson

Goldfine

1982

Science

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The activity of nucleoside triphosphatase, an enzyme that regulates nuclear messenger RNA transport, was measured in highly purified nuclear envelopes isolated from rat liver. Addition of picomolar concentrations of insulin to freshly prepared nuclear envelopes directly increased the enzyme activity. The major effect of insulin on this enzyme was to increase the maximum velocity of its activity; no significant effects were seen on the affinity constant. These studies raise the possibility, therefore, that the nuclear envelope is a site where insulin regulates nuclear functions.

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Section: Insulin Stimulation Of Nucleoside Triphosphatase Activity Insupporting

confidence: 87%

Section: Insulin Stimulation Of Nucleoside Triphosphatase Activity Inmentioning

confidence: 57%

Insulin Stimulation of Nucleoside Triphosphatase Activity in Isolated Nuclear Envelopes

Vigneri

Clawson

Goldfine

1982

Science

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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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“…There are a number of reports demonstrating that insulin increases mRNA levels in liver and other tissues (21)(22)(23)(24)(25)(26)(27)(28)(29). Further, it has recently been reported that the direct addition of insulin to isolated nuclei stimulates the release of mRNA (30). These observations suggest, therefore, that one action of insulin on the nucleus is to regulate mRNA metabolism.…”

mentioning

confidence: 88%

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

Purrello¹,

Burnham²,

Goldfine³

1983

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

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The direct addition of insulin to highly purified nuclear envelopes prepared from the livers of diabetic rats resulted in a decrease in the incorporation of 32p into trichloroacetic acid-precipitable proteins. Autoradiography of 32P-labeled envelopes, solubilized in sodium dodecyl sulfate and subjected to electrophoresis, revealed that insulin decreased the phosphorylation of all major protein bands. Insulin produced detectable effects at concentrations between 0.1 and 1 pM, maximal effects at 10 pM, and progressively diminished effects at higher concentrations. Two insulin analogs, desdipeptide proinsulin and desoctapeptide insulin, had approximately 10% and 1%, respectively, the activity of native insulin. When nuclear envelopes were first phosphorylated with [y-32P]ATP and insulin was then added with an excess of unlabeled ATP, dephosphorylation was enhanced, suggesting that insulin was regulating nuclear envelope phosphatase activity. The direct addition of insulin to isolated rat liver nuclei in the presence of ATP stimulated the release of previously '4C-labeled trichloroacetic acid-precipitable mRNA-like material, and the direct addition of insulin to nuclear envelopes stimulated the activity of nucleoside triphosphatase, the enzyme that participates in mRNA nucleocytoplasmic transport. Moreover, the dose-response curves for these functions mirrored insulin's inhibition of nuclear envelope phosphorylation. These data suggest, therefore, a mechanism whereby insulin directly inhibits the phosphorylation of the nuclear envelope, leading in turn to the regulation of mRNA metabolism.Insulin has numerous effects on target cells, including regulation of membrane transport, enzyme activities, and DNA and RNA metabolism (1, 2). There is evidence that insulin, like other hormones, regulates a number of cellular functions by phosphorylation and dephosphorylation reactions (3-6). Moreover, effects of insulin on phosphorylation and dephosphorylation have recently been observed in broken cell preparations (7-11).We and others have demonstrated specific high-affinity binding sites for insulin on nuclei and nuclear envelopes of liver and other tissues (12)(13)(14)(15)(16)(17). Moreover, morphological studies have suggested that insulin can enter intact cells and interact with the nuclear envelope (18)(19)(20). However, the exact role of insulin in nuclear functions is unknown. There are a number of reports demonstrating that insulin increases mRNA levels in liver and other tissues (21)(22)(23)(24)(25)(26)(27)(28)(29). Further, it has recently been reported that the direct addition of insulin to isolated nuclei stimulates the release of mRNA (30). These observations suggest, therefore, that one action of insulin on the nucleus is to regulate mRNA metabolism.Several lines of evidence indicate that transport of mRNA from the nucleus is mediated by a specific enzyme of the nuclear envelope, the nuclear envelope nucleoside triphosphatase (NTPase; EC 3.6-. (39). Accordingly, in the present study we have investigated ...

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Insulin-modulated transport of RNA from isolated liver nuclei

Cited by 52 publications

References 24 publications

Insulin Stimulation of Nucleoside Triphosphatase Activity in Isolated Nuclear Envelopes

Insulin Stimulation of Nucleoside Triphosphatase Activity in Isolated Nuclear Envelopes

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

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

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