[Study of auricular fibrillation].
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Atrial Fibrillation↗
Biomedical subjects
R G MacDonald
Publications and source records attributed to R G MacDonald.
Estradiol and triiodothyronine increase production of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) by GH4C1 rat pituitary tumor cells.
The main purpose of this study was to examine the effect of 17 beta-estradiol (E2) on the production of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) by GH4C1 cells, a pituitary tumor cell line that displays many phenotypic properties of the anterior pituitary lactotroph. At a low population density (10,500 cells/cm2), E2 stimulated production of IGF-I by 4.2-fold. At this density, the antiestrogen tamoxifen (TAM) had no significant effect, whereas triiodothyronine (T3), which has been demonstrated to increase the level of IGF-I mRNA in the parental GH3 cell line, stimulated IGF-I production by 3.3-fold. Both E2 and T3 also stimulated GH4C1 cell proliferation at this population density. At a four-fold higher population density (42,000 cells/cm2), E2, TAM and T3 had little effect on IGF-I production. E2 failed to stimulate proliferation of GH4C1 cells at high density, and T3 stimulated proliferation to a lesser extent than observed at the low density. At the low population density, E2 and T3 stimulated production of IGFBP-3 by 6- and 11-fold, respectively. At high density, the abilities of E2 and T3 to stimulate IGFBP-3 production were somewhat reduced. TAM had no effect on IGFBP-3 production at either population density. These data indicate that E2 and T3 stimulate production by GH4C1 cells of IGF-I through a mechanism that is sensitive to changes in population density.
Animals↗
Growth stimulation by transfection of intestinal epithelial cells with an antisense insulin-like growth factor binding protein-2 construct.
IEC-6 cells, an intestinal epithelial cell line, produce insulin-like growth factor (IGF)-II and IGF-binding protein-2 (IGFBP-2). Exogenous IGFs stimulate and IGFBP-2 attenuates DNA synthesis. To investigate whether endogenously secreted IGFBP-2 inhibits proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA antisense expression construct. The steady-state level of IGFBP-2 mRNA decreased by 54% in the antisense cDNA-transfected cells (denoted revBP2) compared with vector-transfected controls. Moreover, revBP2 cells secreted less IGFBP-2 than controls (maximally a 68% decrease). In serum-containing medium, revBP2 cells exhibited a 35% increase in log-phase proliferation rate and growth-arrested at a maximum density 14% higher than controls. We conclude that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs.
Animals↗
Distribution of insulin-like growth factor receptors in rat intestinal epithelium.
In summary, we present data from affinity cross-linking and Scatchard plot analysis that demonstrates the presence of both IGF-I receptors and IGF-II receptors on the brush border membranes of rat intestinal mucosa. The brush border location of the IGF receptors suggests that IGFs available in the intestinal lumen may initiate signal transduction events by binding to receptors displayed on the mucosal lining. Our findings provide further support for the notion that at least some of the mitogenic stimulus for rapid proliferation of intestinal epithelium arises from lumenal IGFs, which may be supplied by apical secretions from the mucosa, or in saliva, colostrum, milk, chyme, or bile.
Animals↗
Localization of the insulin-like growth factor II (IGF-II) binding/cross-linking site of the IGF-II/mannose 6-phosphate receptor to extracellular repeats 10-11.
The insulin-like growth factor II (IGF-II) binding/cross-linking domain of the IGF-II/Man-6-P receptor was mapped by sequencing receptor fragments covalently attached to IGF-II. Rat placental or bovine liver receptors were purified by pentamannosyl-6-phosphate-Sepharose chromatography, affinity-labeled with 125I-IGF-II using disuccinimidyl tartrate, and digested with endoproteinase Glu-C. Analysis of small scale digests by gel electrophoresis revealed radiolabeled bands of approximately 17 kDa (rat) or approximately 18 kDa (bovine). For purification and sequencing of these radiolabeled receptor fragments, three receptor preparations were analyzed. The initial digests were fractionated by gel filtration followed by reverse-phase high performance liquid chromatography (HPLC), but the final purification steps differed somewhat in the three studies, using combinations of two-dimensional HPLC, gel electrophoresis, and electroblotting. Multiple sequences detected in each of these samples were unscrambled by computer-assisted and manual methods and by comparison with the quantity of labeled IGF-II present to identify sequences corresponding to fragments of the receptor covalently attached to IGF-II. The sequence, S(H)VNSXPMF, located in the COOH-terminal end of extracellular repeat 10 and beginning with serine 1488 of the bovine receptor, was the only receptor sequence common to all the samples and was the best candidate for the IGF-II cross-linked peptide by quantitative analysis. These data indicate residues within repeats 10-11 are likely to be important for IGF-II binding. We conclude that cross-linking between IGF-II and its receptor involves one or more of the 4 lysine residues located within extracellular repeat 11.
Affinity Labels↗
Neuropeptide Y promotes GTP photo-incorporation into a 55 kDa protein.
Incubation of bovine hippocampal membranes with [alpha-32P]GTP and exposure to ultraviolet light resulted in the labelling of seven species with apparent molecular masses of 200, 74, 55, 53, 50, 43 and 40 kDa. Labelling of the 55 kDa species was greatly enhanced in the presence of carboxyl terminal fragments [neuropeptide Y-(18-36)] of neuropeptide Y. Labelling occurred with [alpha-32P]GTP but not [alpha-32P]ATP. A group of putative direct G protein activating peptides including mastoparan, melittin, substance P and adrenocorticotropic hormone (ACTH)-(1-24), were also able to stimulate the labelling of this protein. Labelling of the 55 kDa protein could be demonstrated in bovine brain but not peripheral tissues. Western blot analysis using an antibody against the common alpha subunit of G proteins recognized a protein co-migrating with the 55 kDa GTP-binding protein. These findings demonstrate the existence of a previously uncharacterized neuronal protein, with an apparent molecular mass of 55 kDa, that binds GTP in response to neuropeptide Y and other peptides.
Affinity Labels↗
Rat liver cytosolic 4 S polycyclic aromatic hydrocarbon-binding protein is glycine N-methyltransferase.
In the rat, cytochrome P-450IA1 gene expression, which is most closely associated with aryl hydrocarbon hydroxylase activity, is thought to be regulated by several trans-acting factors, including the 4 S polycyclic aromatic hydrocarbon (PAH)-binding protein. This protein has been purified to homogeneity from rat liver using ion exchange, gel permeation, hydrophobic interaction, and affinity chromatographies. Partial sequencing of the 33-kDa band indicated its identity as glycine N-methyltransferase (GNMT). Polyclonal antibodies to GNMT immunoprecipitated PAH-binding activity from rat liver cytosol. Methyltransferase and PAH-binding activities copurified during the course of protein purification. GNMT protein and PAH binding activity were colocalized in various cytosolic fractions. These data all indicate that the 4 S PAH-binding protein and GNMT are one and the same protein or very similar proteins. Western blot analyses yielded a positive signal under denaturing (33 kDa) and nondenaturing (150 kDa, tetramer) conditions; the PAH-binding protein also was an oligomer. GNMT was detected by immunohistochemistry in nuclei from H4IIE rat hepatoma cells and rat liver. The localization of GNMT in liver nuclei is in accordance with a role in modulating cytochrome P-450IA1 gene expression.
Amino Acid Sequence↗
Coronary artery fistula as a complication of percutaneous transluminal coronary angioplasty.
A patient underwent successful percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending and the right coronary arteries for worsening angina and was discharged without any apparent complication. Repeat cardiac catheterization, done four weeks later for recurrent angina, showed a coronary artery fistula to the right ventricle at the site of moderately severe subintimal dissection. The patient was managed conservatively. At cardiac catheterization 18 months after the PTCA procedure, there was no evidence of the fistula.
Angina Pectoris↗
Role of sulfhydryl groups in Y2 neuropeptide Y receptor binding activity.
Benextramine, a tetramine disulfide, irreversibly inhibits neuropeptide Y (NPY) binding to the 50-kDa Y2 NPY receptor in bovine hippocampus (Li, W., MacDonald, R. G., and Hexum, T. D. (1991) Eur. J. Pharmacol. 207, 89-91). Evidence is presented that this inhibition occurs through a thiol-disulfide exchange. Treatment of bovine hippocampal membranes with benextramine inhibited NPY affinity cross-linking to the 50-kDa receptor. This inhibition of labeling was not affected by washing the membranes, but could be completely reversed by the addition of several thiol reducing reagents, including reduced glutathione, beta-mercaptoethanol, and cysteine. Benextramine inhibited 70% of NPY-specific labeling and was much more effective than other sulfhydryl reactive agents, such as oxidized glutathione, cystamine, and 5,5'-dithio-bis(2-nitrobenzoic acid). Furthermore, the sulfhydryl-modifying agents N-ethylmaleimide and p-chloromercuriphenyl-sulfonic acid specifically decreased NPY affinity labeling. Finally, NPY labeling of the 50-kDa receptor was reduced by the heavy metal ions Zn2+, Cu2+, and Hg2+. Preincubation with NPY prevented Y2 receptors from being inactivated by either 400 microM N-ethylmaleimide or 1 mM benextramine. These results suggest that one or more benextramine-sensitive sulfhydryl groups on the Y2 receptor are important for NPY binding activity.
Adrenergic alpha-Antagonists↗
Neuropeptide Y receptor in bovine hippocampus is a Y2 receptor.
[125I]NPY bound to a single class of saturable binding sites on bovine hippocampus membranes with a KD of 0.1 mM and Bmax of 165 fmol/mg of protein. The rank order of potency of NPY fragments and other structurally related peptides to inhibit [125I]NPY binding was: PYY greater than or equal to NPY much greater than BPP greater than or equal to APP and NPY greater than NPY-(13-36) greater than NPY-(18-36) greater than or equal to NPY-(20-36) much greater than NPY-(26-36) greater than NPY-(free acid). The identity of the NPY binding site was investigated by affinity labeling. Gel electrophoresis followed by autoradiography revealed a band with a mol mass of 50 kDa. Unlabeled NPY or PYY, but not BPP, HPP and APP, inhibited labeling of [125I]NPY to the 50 kDa protein band. Moreover, labeling was inhibited by NPY greater than NPY-(18-36) greater than or equal to NPY-(13-36) greater than or equal to NPY-(20-36) greater than NPY-(26-36) greater than NPY-(free acid). The binding of [125I]NPY and the intensity of the cross-linked band were reduced in parallel by increasing concentrations of unlabeled NPY (IC50 = 0.7 nM and 0.6 mM, respectively). These studies demonstrate that bovine hippocampal membranes contain a 50 kDa [125I]NPY binding site that has the ligand specificity characteristic of the Y2 receptor subtype.
Affinity Labels↗
Secretion of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 by intestinal epithelial (IEC-6) cells: implications for autocrine growth regulation.
To identify the factors regulating the proliferation of intestinal epithelium, we examined the effects of various growth factors on [3H] thymidine incorporation into the DNA of IEC-6 cells, an intestinal epithelial cell line derived from rat jejunal crypts. Insulin-like growth factor-I (IGF-I), IGF-II, and insulin stimulated the DNA and protein synthesis of IEC-6 cells in serum-free medium supplemented with transferrin, dexamethasone, and BSA (basal medium). Concentration-response experiments demonstrated that IGF-I is approximately 10 times more potent than IGF-II or insulin in producing 2- to 3-fold stimulations of DNA and protein synthesis by IEC-6 cells. In addition, IEC-6 cells proliferated slowly in the basal medium without any added growth factors. Analysis of medium conditioned by IEC-6 cells by gel filtration chromatography, RIA, HPLC, and N-terminal sequencing revealed that IEC-6 cells synthesize and secrete mature, 7,500 mo wt (M(r)) IGF-II as well as high M(r) forms of IGF-II. In addition, ligand blot, immunoblot, and N-terminal sequence analyses showed that IEC-6 cells produce the 34,000 M(r) IGF-binding protein-2 (IGFBP-2). To determine if IGFBP-2 modulates IGF responses in IEC-6 cells, the IGF-I analogs, Des-(1-3)-IGF-I and [Gln3,Ala4,Tyr15,Leu16]IGF-I, both of which have a reduced affinity for IGFBPs, were tested for their effects on IEC-6 cell proliferation. Both analogs exhibited 10-fold greater potency than IGF-I, presumably because endogenously secreted IGFBPs depress IGF-I binding to cell surface receptors. Finally, purified IGFBP-2 attenuated the DNA synthesis of IEC-6 cells in a dose-dependent manner. We conclude that IGFBP-2 secreted by intestinal epithelial cells is capable of limiting the mitogenic activity of both exogenous and endogenous IGFs by blocking the association of the growth factors with cell surface binding sites. These results further suggest that the growth of IEC-6 cells is modulated by autocrine mechanisms involving IGF-II and IGFBP-2.
Amino Acid Sequence↗
Benextramine irreversibly inhibits [125I]neuropeptide Y affinity labeling of the Y2 binding protein in bovine hippocampus.
Affinity labeling of iodinated neuropeptide Y (NPY) to bovine hippocampal binding proteins revealed that benextramine inhibited specific NPY labeling of the 50 kDa NPY binding protein (Y2 binding protein) in a dose-dependent manner (IC50 = 33 microM). Hippocampal membranes, which were pretreated with benextramine and washed, exhibited decreased [125I]NPY labeling of binding proteins in a similar dose-dependent manner. These findings demonstrate that benextramine irreversibly blocks specific NPY binding to the 50 kDa NPY Y2 binding protein.
Affinity Labels↗
Clinical and angiographic determinants of primary coronary angioplasty success. M-HEART Investigators.
Clinical and anatomic determinants of the initial success of percutaneous transluminal coronary angioplasty were prospectively evaluated in 826 patients enrolled in the Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART). The 639 men and 187 women ranged in age from 31 to 85 years. Successful angioplasty (residual stenosis less than 50% and no major complications) was achieved in 886 (88.6%) of 1,000 lesions. Success rates were uniform among the eight individual centers. Outcome was not influenced by gender, age or other clinical features, including severity and duration of angina, prior myocardial infarction, rest pain, transient ST segment elevation, history of smoking or diabetes. In contrast, procedural outcome was significantly associated with lesion-specific angiographic factors. Stenoses 60% to 74%, 75% to 89%, 90% to 99% and 100% were associated with success rates of 96%, 90%, 84% and 69%, respectively (p less than 0.001). Angioplasty was less successful in calcified than in noncalcified lesions (82% versus 90%, p less than 0.01), in thrombotic than in nonthrombotic lesions (82% versus 90%, p less than 0.05) and in lesions in the right coronary artery than in other vessels (84% versus 90%, p less than 0.01). Outcome was not related to other anatomic variables, including lesion location (proximal versus distal), vessel size, eccentricity, stenosis length or translesional gradient. By multivariate logistic regression, preangioplasty percent stenosis, right coronary artery location and lesion calcification were demonstrated to be significant independent predictors of angioplasty success. Alternative clinical and angiographic variables did not contribute to this regression model.(ABSTRACT TRUNCATED AT 250 WORDS)
Angioplasty, Balloon, Coronary↗
Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators.
The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (less than or equal to 4.6 mm, 33%; greater than 4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (less than or equal to 73%, 25%; greater than 73%, 43%; p = 0.005), percent stenosis after angioplasty (less than or equal to 21%, 33%; greater than 21%, 46%; p = 0.017) and arterial diameter (less than 2.9 mm, 44%; greater than or equal to 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and "optimal" balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis.
Angioplasty, Balloon, Coronary↗
Automated microparticle enzyme immunoassays for IgG and IgM antibodies to Toxoplasma gondii.
Fully automated microparticle enzyme immunoassays (MEIA) for the IMx immunoassay analyser were developed to detect IgG and IgM antibodies to Toxoplasma gondii. The IgG MEIA results are expressed in International Units (IU) of IgG antibody interpolated from a six point calibration curve covering the range from 0 to 300 IU/ml. Reproducible results were obtained from a calibration curve stored in the instrument for at least one month. The qualitative IgM MEIA expresses results as an index using a single calibrator included in each run. The Toxo IgG MEIA and Toxo IgM MEIA were in 98% and 97% agreement, respectively, with the reference assays used. Twenty four sera can be completely processed in about 35 minutes.
Animals↗
Mannose-6-phosphate enhances cross-linking efficiency between insulin-like growth factor-II (IGF-II) and IGF-II/mannose-6-phosphate receptors in membranes.
Endogenous and exogenous phosphomannosyl ligands inhibit binding of insulin-like growth factor-II (IGF-II) to the IGF-II/mannose-6-phosphate receptor (IGF-II/Man-6-P receptor). In the present study, the mechanism of this antagonism was examined using a [125I]IGF-II cross-linking assay with disuccinimidyl suberate in cell membranes. Treatment with 5 mM Man-6-P enhanced [125I]IGF-II cross-linking to the receptor. The magnitude of the Man-6-P enhancement differed depending on the source of the membranes, ranging from a 30% increase in JEG-3 human choriocarcinoma up to a 560% increase in B16-F1 mouse melanoma. Man-6-P stimulated [125I]IGF-II-receptor cross-linking in H-35 hepatoma membranes by about 80%, even at concentrations of labeled IGF-II (greater than or equal to 10 nM) that nearly saturated the receptors. Thus, in addition to its effect on IGF-II-binding affinity, Man-6-P caused a 1.5- to 2-fold increase in cross-linking efficiency within the IGF-II-receptor complex. Furthermore, Man-6-P enhanced [125I]IGF-II cross-linking to the H-35 receptor by a constant (approximately 80%) increment 1) when the cross-linking reaction was conducted in buffers of different pH over the range 6.8-8.0, or 2) using cross-linking agents differing in spacer arm length from 6.4-16.1 A. Washing membranes before assay with either Man-6-P (pH 7.4) or 0.5 M NaCl (pH 4.5) reduced the subsequent Man-6-P enhancement of [125I]IGF-II-receptor cross-linking, suggesting that this phenomenon was actually due to displacement of inhibitory phosphomannosyl ligands bound endogenously to the Man-6-P sites of the receptor. In support of this hypothesis, Man-6-P produced a minimal (8-14%) enhancement of [125I]IGF-II-receptor cross-linking in membranes from I-cell fibroblasts lacking such phosphomannosyl ligands. Thus, phosphomannosyl ligands bound to the IGF-II/Man-6-P receptor decrease both IGF-II-binding affinity and IGF-II-receptor cross-linking efficiency. Membrane-associated receptors appear to exist in experimentally and perhaps functionally distinct populations, depending on occupancy of the Man-6-P-binding sites.
Animals↗
Insulin action on activity and cell surface disposition of human HepG2 glucose transporters expressed in Chinese hamster ovary cells.
Complementary DNA encoding a facilitative glucose transporter was isolated from a human hepatoma cell line (HepG2) cDNA library and subcloned into a metal-inducible mammalian expression vector, pLEN (California Biotechnology) containing human metallothionein gene II promoter sequences. Chinese hamster ovary (CHO) cells transfected with this transporter expression vector, pLENGT, exhibited a 2-17-fold increase in immunoreactive HepG2-type glucose transporter protein, as measured by protein immunoblotting with antipeptide antibodies directed against the HepG2-type glucose transporter C-terminal domain. Expression of the human glucose transporter was verified by protein immunoblotting with a mouse polyclonal antiserum that recognizes the human but not the rodent HepG2-type transporter. 2-Deoxy-D-glucose uptake was increased 2-7-fold in transfected cell lines. Polyclonal antisera directed against purified red blood cell glucose transporter were raised in several rabbits. Antiserum from one rabbit, delta, was found to bind to the surface of intact red cells but not to inside-out red cell ghosts. Using this delta-antiserum in intact cell-binding assays, 1.6-9-fold increases in cell surface expression of the human glucose transporter were measured in CHO-K1 cell lines transfected with the transporter expression vector. Measurements of total cellular glucose transporter immunoreactive protein using anti-HepG2 transporter C-terminal peptide serum, cell surface glucose transporter protein using delta-antiserum and 2-deoxyglucose uptake revealed proportional relationships among these parameters in transfected cell lines expressing different levels of transporter protein. Insulin increased 2-deoxyglucose uptake 40% in control CHO-K1 cells and in CHO-K1 cells expressing modest levels of the human glucose transporter protein. However, stimulation of sugar-uptake by insulin was only 10% in cells overexpressing human glucose transporter protein 9-fold, and no effect of insulin on sugar uptake was detected in several cell lines expressing very high levels (12-17-fold over controls) of human HepG2 glucose transporter protein. No insulin stimulation of anti-cell surface glucose transporter antibody binding was detected in any control or transfected CHO-K1 cell lines. These data indicate that a glucose transporter protein that is insensitive to insulin in HepG2 cells is regulated by insulin when expressed at low but not at high levels in insulin-response CHO-K1 cells. Additionally, the results suggest that insulin does not increase 2-deoxyglucose uptake by increasing the number of cell surface HepG2-type glucose transporters in CHO-K1 fibroblasts.
Animals↗
Insulin-sensitive phosphorylation of serine 1293/1294 on the human insulin receptor by a tightly associated serine kinase.
In these studies we demonstrate that insulin stimulates both tyrosine and serine phosphorylation of the insulin receptor after its partial purification on wheat germ-agarose, and after affinity purification on insulin-agarose. Analysis of the serine phosphate incorporated into partially purified or highly purified insulin receptor suggests that an insulin-sensitive serine kinase (IRSK) copurifies with the insulin receptor. Following trypsin digestion, reversed-phase high pressure liquid chromatography (HPLC) analysis of the phosphorylated, affinity-purified insulin receptor preparation reveals phosphopeptide profiles similar to those of trypsin-digested receptors immunoprecipitated from 32P-labeled fibroblasts overexpressing the human insulin receptor. The major insulin-stimulated HPLC phosphopeptide peak from insulin receptors labeled in intact cells contains a hydrophilic phosphoserine-containing peptide which rapidly elutes from a C18 column. HPLC and two-dimensional separation indicate that the same phosphopeptide is obtained when affinity-purified insulin receptors are phosphorylated by IRSK. The serine containing tryptic peptide within the cytoplasmic domain of the human insulin receptor predicted to elute most rapidly upon HPLC had the sequence SSHCQR corresponding to residues 1293-1298. A synthetic peptide containing this sequence is phosphorylated by the insulin receptor/IRSK preparation. After alkylation and trypsin digestion, the synthetic phosphopeptide comigrates with the alkylated, tryptic phosphopeptide derived from insulin receptor phosphorylated in vitro by IRSK. We propose that serine 1293 or 1294 of the human insulin receptor is a major site(s) phosphorylated on the insulin receptor in intact cells and is phosphorylated by IRSK. Furthermore, insulin added directly to affinity-purified insulin receptor/IRSK preparations stimulates the phosphorylation of synthetic peptides corresponding to this receptor phosphorylation site and another containing threonine 1336. Kemptide phosphorylation is not stimulated by insulin under these conditions. No phosphorylation of peptide substrates for Ca2+/calmodulin-dependent protein kinase, protein kinase C, casein kinase II, or cGMP-dependent protein kinase by IRSK is detected. These data indicate that IRSK exhibits specificity for the insulin receptor and may be activated by the insulin receptor tyrosine kinase in an insulin-dependent manner.
Amino Acids↗