The insulin receptor tyrosyl kinase phosphorylates holomeric forms of the guanine nucleotide regulatory proteins G<sub>i</sub> and G<sub>o</sub>

O’Brien, Richard M.; Houslay, Miles D.; Milligan, Graeme; Siddle, Kenneth

doi:10.1016/0014-5793(87)81361-3

Cited by 125 publications

(47 citation statements)

References 31 publications

(7 reference statements)

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“…Similarly, we [5] and others [6] have shown that incubation of pure preparations of Gi and Go with a purified human insulin receptor preparation leads to the phosphorylation of ce-Gi. It has been suggested that phosphorylation of Gi by protein kinase C may lead to its inactivation as incubation of platelets with tumour promoting phorbol esters, which activate protein kinase C, blocked the ability of CeE-adrenoceptors to inhibit adenylate cyclase activity [7].…”

Section: Introductionsupporting

confidence: 64%

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein G_i

et al. 1989

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The antiserum AS7 can specifically immunopreeipitate a-Gi from membrane extracts as well as from a mixture of purified ct-Gi and a-Go as ascertained using [azP]ADP-ribosylated G-proteins. Using this antiserum to immunopreeipitate ~t-G~ from hepatocytes labelled with a2p it was evident that ~t-Gi was phosphorylated under basal (resting) conditions. Challenge of hepatocytes with the tumour promoting phorbol ester TPA, however, elicited a marked enhancement of the phosphorylation state of ~t-Gi. This was accompanied by the loss of inhibitory effect of G~ on adenylate cyclase, as judged by the inability of low concentrations of p[NH]ppG to inhibit forskolin-stimulated adenylate cyclase activity. Such actions were mimicked by treatment of hepatocytes with either glucagon or TH-glucagon, an analogue of glucagon which is incapable of activating adenylate cyclase and elevating intracellular cyclic AMP concentrations. Pre-treatment of hepatocytes with either glucagon, TPA or insulin did not affect the ability of pertussis toxin to cause the NAD +-dependent, [azP]ADP-ribosylation of a-Ga in membrane fractions isolated from such pre-treated hepatocytes. We suggest that protein kinase C can elicit the phosphorylation and functional inactivation of ~t-G~ in intact hepatoeytes. As pertussis toxin only causes the ADP-ribosylation of the holomeric form of G~, it may be that phosphorylation leaves ct-Gi in its holomeric state.

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Section: Introductionsupporting

confidence: 64%

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein G_i

et al. 1989

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“…These authors showed that insulin-dependent lipolysis and inhibition of glucose oxidation in adipocytes were blocked by pertussis toxin. Following this original observation, there were several reports that suggested that the insulin receptor phosphorylates G␣ i and G␣o (O'Brien et al, 1987;Krupinski et al, 1988) and that the insulin receptor is coupled to G proteins of the Gi family (Rothenberg and Kahn, 1988;Ciaraldi and Maisel, 1989). These studies were followed by reports of G proteins associated with the insulin receptor (Jo et al, 1992(Jo et al, , 1993 and the identification of regions within the insulin receptor that can activate heterotrimeric G proteins .…”

Section: B Insulin and Insulin-like Growth Factor Receptorsmentioning

confidence: 97%

Single Transmembrane Spanning Heterotrimeric G Protein-Coupled Receptors and Their Signaling Cascades

Patel

2004

Pharmacol Rev

101

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“…Phosphorylation of G proteins by, for example, protein kinases C1C. W.Taylor C (Sagi-Eisenberg, 1989: Pyne et al, 1989 or receptor tyrosine kinases (Zick et al, 1986;Valentine-Braun et al, 1986;O'Brien et al, 1987) (Jakobs et al, 1985).…”

Section: G Proteins Remembermentioning

confidence: 99%

The role of G proteins in transmembrane signalling

Taylor

1990

Biochemical Journal

226

113

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INTRODUCTIONIn some transmembrane signalling systems detection of the extracellular stimulus and generation of an intracellular response are properties of the same protein or protein complex. Binding of acetylcholine to the a subunits of the pentameric nicotinic receptor, for example, opens a cation-selective channel formed by parts of each of the receptor subunits, and insulin when it binds to the extracellular domain of its receptor activates a protein tyrosine kinase activity in the intracellular domain of the same protein. Rodbell and his collaborators (Rodbell et al., 1971) were the first to provide evidence for a more complex class of signalling pathway where the sensor and intracellular effector are separate proteins that communicate through a guanine nucleotide-dependent regulatory protein or G protein. The G protein cycles between inactive GDP-bound and active GTPbound forms. Activation is catalysed by receptors and deactivation is an intrinsic property of the G protein, its GTPase activity. The developments that followed Rodbell's pioneering studies have established that many different receptors regulate many intracellular effectors through a family of closely related G proteins (Citri & Schramm, 1980;Rodbell, 1980;Schramm & Selinger, 1984;Northup, 1985;Levitzki, 1988). Many excellent recent reviews have focused on various aspects of these interactions between receptors, G proteins and intracellular effectors (Casperson & Bourne, 1987;Gilman, 1987;Allende, 1988;Lochrie & Simon, 1988;Weiss et al., 1988;Chabre & Deterre, 1989;Ross, 1989;Houslay, 1990).The G protein cycle, at the centre of the conversation between receptors and their effectors, provides one solution to the compromise that cells must make between responding rapidly and being able to respond to very low concentrations of extracellular stimulus. In this review I will consider how different signalling mechanisms are adapted to the cellular processes they control by comparing the properties of the signalling pathways that involve G proteins with the simpler pathways that do not.

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The insulin receptor tyrosyl kinase phosphorylates holomeric forms of the guanine nucleotide regulatory proteins G_i and G_o

Cited by 125 publications

References 31 publications

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein G_i

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein G_i

Single Transmembrane Spanning Heterotrimeric G Protein-Coupled Receptors and Their Signaling Cascades

The role of G proteins in transmembrane signalling

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The insulin receptor tyrosyl kinase phosphorylates holomeric forms of the guanine nucleotide regulatory proteins Gi and Go

Cited by 125 publications

References 31 publications

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein Gi

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein Gi

Single Transmembrane Spanning Heterotrimeric G Protein-Coupled Receptors and Their Signaling Cascades

The role of G proteins in transmembrane signalling

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About

The insulin receptor tyrosyl kinase phosphorylates holomeric forms of the guanine nucleotide regulatory proteins G_i and G_o

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein G_i

Treatment of intact hepatocytes with either the phorbol ester TPA or glucagon elicits the phosphorylation and functional inactivation of the inhibitory guanine nucleotide regulatory protein G_i