Calmodulin as substrate for insulin-receptor kinase. Phosphorylation by receptors from rat skeletal muscle

To see if insulin receptor kinase activity alters with aging, the activity of wheat germ agglutinin-purified receptor preparations from liver and skeletal muscle was compared in 2-, 4-, 10-, and 20-mo-old rats. Basal and insulin-stimulated autophosphorylation of liver insulin receptor and its kinase activities toward histone 2b and poly(Glu4Tyr1) did not alter with aging. On the other hand, the muscle insulin receptor showed different results. Insulin-stimulated increases of autophosphorylation and the kinase activity toward histone 2b above basal were comparable in the four groups. However, insulin-stimulated phosphorylation of poly(Glu4Tyr1) was decreased in 20-mo-old rats compared with 10- and 4-mo-old rats. These results indicate that insulin receptor kinase activity could vary under certain conditions, depending on the substrate used to measure the activity. It is concluded that insulin receptor kinase activity does not change markedly during the process of aging, although subtle changes seem to exist.

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In vitro and in vivo activation of the insulin receptor kinase in control and denervated skeletal muscle.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)84478-2 ◽

1986 ◽

Vol 261 (19) ◽

pp. 8985-8993

Author(s):

C F Burant ◽

M K Treutelaar ◽

M G Buse

Keyword(s):

Skeletal Muscle ◽

Insulin Receptor ◽

Receptor Kinase ◽

Insulin Receptor Kinase

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Role of human skeletal muscle insulin receptor kinase in the in vivo insulin resistance of noninsulin-dependent diabetes mellitus and obesity.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.78.2.8106637 ◽

1994 ◽

Vol 78 (2) ◽

pp. 471-477

Author(s):

J J Nolan ◽

G Freidenberg ◽

R Henry ◽

D Reichart ◽

J M Olefsky

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Receptor ◽

Human Skeletal Muscle ◽

Dependent Diabetes Mellitus ◽

Receptor Kinase ◽

Insulin Receptor Kinase

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Insulin receptor kinase is hyperresponsive in adipocytes of young obese Zucker rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.2.e273 ◽

1987 ◽

Vol 252 (2) ◽

pp. E273-E278 ◽

Cited By ~ 1

Author(s):

A. Debant ◽

M. Guerre-Millo ◽

Y. Le Marchand-Brustel ◽

P. Freychet ◽

M. Lavau ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Receptor ◽

Insulin Action ◽

Kinase Activity ◽

Insulin Receptors ◽

Zucker Rats ◽

Receptor Kinase ◽

Insulin Receptor Tyrosine Kinase ◽

Obese Zucker Rats ◽

Insulin Receptor Kinase

Thirty-day-old obese Zucker rats have hyperresponsive adipose tissue, whereas their skeletal muscle normally responds to insulin in vitro. To further substantiate the role of insulin receptor tyrosine kinase in insulin action, we have studied the kinase activity of receptors obtained from adipocytes and skeletal muscle of these young obese Zucker rats. Insulin receptors, partially purified by wheat germ agglutinin agarose chromatography from plasma membranes of isolated adipocytes or from skeletal muscles, were studied in a cell-free system for auto-phosphorylation and for their ability to phosphorylate a synthetic glutamate-tyrosine copolymer. For an identical amount of receptors, the insulin stimulatory action on its beta-subunit receptor phosphorylation was markedly augmented in preparations from hyperresponsive adipocytes of obese animals compared with lean rats. Basal phosphorylation of adipocyte insulin receptors was nearly identical in lean and obese animals. Similarly the capacity of adipocyte insulin receptors to catalyze the phosphorylation of the synthetic substrate in response to insulin was increased. By contrast, the kinase activity of insulin receptors prepared from normally insulin-responsive skeletal muscle was similar in preparations of lean and obese rats. These results show that a state of hyperresponsiveness to insulin is correlated with a parallel increase of insulin receptor kinase activity suggesting an important role for this activity in insulin action.

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Skeletal muscle insulin-receptor kinase. Effects of substrate inhibition and diabetes

Diabetes ◽

10.2337/diabetes.40.12.1691 ◽

1991 ◽

Vol 40 (12) ◽

pp. 1691-1700 ◽

Cited By ~ 1

Author(s):

N. E. Block ◽

K. Komori ◽

S. L. Dutton ◽

K. A. Robinson ◽

M. G. Buse

Keyword(s):

Skeletal Muscle ◽

Insulin Receptor ◽

Substrate Inhibition ◽

Receptor Kinase ◽

Insulin Receptor Kinase

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Delayed onset of insulin activation of the insulin receptor kinase in vivo in human skeletal muscle

Diabetes ◽

10.2337/diabetes.43.1.118 ◽

1994 ◽

Vol 43 (1) ◽

pp. 118-126 ◽

Cited By ~ 3

Author(s):

G. R. Freidenberg ◽

S. Suter ◽

R. R. Henry ◽

J. Nolan ◽

D. Reichart ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Receptor ◽

Human Skeletal Muscle ◽

Receptor Kinase ◽

Delayed Onset ◽

Insulin Receptor Kinase

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Insulin activates GTP binding to a 40 kDa protein in fat cells

Biochemical Journal ◽

10.1042/bj2760103 ◽

1991 ◽

Vol 276 (1) ◽

pp. 103-108 ◽

Cited By ~ 21

Author(s):

M Kellerer ◽

B Obermaier-Kusser ◽

A Pröfrock ◽

E Schleicher ◽

E Seffer ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Receptor ◽

Binding Site ◽

G Protein ◽

Plasma Membranes ◽

Fat Cells ◽

Dependent Manner ◽

Receptor Kinase ◽

Gtp Binding ◽

Insulin Receptor Kinase

The first steps in insulin action are binding of insulin to its receptor and activation of the insulin receptor kinase. As there is indirect evidence that further signal transduction might involve a guanine-nucleotide-binding protein (G-protein), we studied whether insulin modulates GTP binding to plasma membrane proteins of fat cells and skeletal muscle. We found that insulin rapidly increased (30 s) binding of guanosine 5′-[gamma-thio]triphosphate (GTP[S]) in a dose dependent manner (0.03-2.0 nM). This effect was not altered by pertussis toxin, but it was abolished by cholera toxin treatment of fat cells. Scatchard analysis of the binding data showed that the increased GTP[S] binding is due to a decrease in the Kd for GTP from 100 nM to 50 nM. Furthermore, binding of GTP to these plasma membranes inhibited both the binding of 125I-insulin to the insulin receptor and the stimulation of the insulin receptor kinase, suggesting a feedback interaction between the insulin-stimulated GTP-binding site and the insulin receptor. In order to identify this insulin-stimulated GTP-binding site, plasma membranes were labelled with the photoreactive GTP analogue [alpha-32P]GTP gamma-azidoanilide. We found that insulin selectively stimulated GTP binding to a 40 kDa protein. In conclusion, in plasma membranes of fat cells and skeletal muscle, the insulin receptor interacts with a 40 kDa GTP-binding site. We speculate that this 40 kDa GTP-binding site might be a G-protein which is involved in insulin signal transmission.

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In vivo insulin mimetic effects of pV compounds: role for tissue targeting in determining potency

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.1.e60 ◽

1995 ◽

Vol 268 (1) ◽

pp. E60-E66 ◽

Cited By ~ 3

Author(s):

A. P. Bevan ◽

J. W. Burgess ◽

J. F. Yale ◽

P. G. Drake ◽

D. Lachance ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Receptor ◽

Glycogen Synthesis ◽

Insulin Receptors ◽

Receptor Kinase ◽

Rat Diaphragm ◽

Insulin Mimetic ◽

Integrated Response ◽

Insulin Receptor Kinase

Peroxovanadium (pV) compounds activate the insulin receptor kinase in hepatocytes and inhibit the dephosphorylation of insulin receptors in hepatic endosomes with highly correlated potencies (Posner, B. I., R. Faure, J. W. Burgess, A. P. Bevan, D. Lachance, G. Zhang-Sun, J. B. Ng, D. A. Hall, B. S. Lum, and A. Shaver J. Biol. Chem. 269: 4596–4604, 1994). After intravenous administration, K2[VO(O2)2(picolinato)].2H2O [bpV(pic)], VO(O2) (picolinato) (H2O)2 [mpV(pic)], K[VO(O2)2(picolinato)].3H2O [bpV(phen)], and K[VO(O2)2(4,7-dimethyl-1,10-phenanthroline)].1/2H2O [bpV(Me2phen)] produced 50% of their maximal hypoglycemic effect at doses of 0.04, 0.04, 0.32, and 0.65 mumol/100 g body wt, respectively. In contrast, their potencies as inhibitors of dephosphorylation were bpV(pic) = bpV(phen) > mpV(pic) = bpV(Me2phen). bpV(pic) stimulated [14C]glucose incorporation into rat diaphragm glycogen in vivo, and its effect was dose dependent, synergistic with insulin, and evident in other skeletal muscles. In contrast, bpV(phen) displayed no effect on glycogen synthesis in skeletal muscle. mpV(pic) stimulated and bpV(Me2phen) had no effect on glycogen synthesis in the diaphragm. bpV(pic) augmented rat diaphragm insulin receptor kinase 2.2-fold with a time-integrated response 70% that of insulin. In contrast, the effect of bpV(phen) was delayed and much reduced. Thus, the in vivo potencies of pV compounds reflect differing capacities to act on skeletal muscle. The ancillary ligand within the pV complex may target one tissue in preference to another.

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