Insulin-like receptor : Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

Gene name - Insulin-like receptor

Synonyms -

Cytological map position -

Function - receptor

Keywords - insulin receptor pathway, growth, survival

Symbol - InR

FlyBase ID: FBgn0283499

Genetic map position -

Classification - protein tyrosine kinase

Cellular location - surface

NCBI links: Precomputed BLAST | Entrez Gene | HomoloGene | UniGene
Recent literature
Lebreton, S., Trona, F., Borrero-Echeverry, F., Bilz, F., Grabe, V., Becher, P. G., Carlsson, M. A., Nassel, D. R., Hansson, B. S., Sachse, S. and Witzgall, P. (2015). Feeding regulates sex pheromone attraction and courtship in Drosophila females. Sci Rep 5: 13132. PubMed ID: 26255707
In Drosophila melanogaster, gender-specific behavioural responses to the male-produced sex pheromone cis-vaccenyl acetate (cVA) rely on sexually dimorphic, third-order neural circuits. This study shows that nutritional state in female flies modulates cVA perception in first-order olfactory neurons. Starvation increases, and feeding reduces attraction to food odour, in both sexes. Adding cVA to food odour, however, maintains attraction in fed females, while it has no effect in males. Upregulation of sensitivity and behavioural responsiveness to cVA in fed females is paralleled by a strong increase in receptivity to male courtship. Functional imaging of the antennal lobe (AL), the olfactory centre in the insect brain, shows that olfactory input to DA1 and VM2 glomeruli is also modulated by starvation. Knocking down insulin receptors in neurons converging onto the DA1 glomerulus suggests that insulin-signalling partly controls pheromone perception in the AL, and adjusts cVA attraction according to nutritional state and sexual receptivity in Drosophila females.
Yu, Y., Huang, R., Ye, J., Zhang, V., Wu, C., Cheng, G., Jia, J. and Wang, L. (2016). Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila. Elife [Epub ahead of print]. PubMed ID: 27612383
Starvation induces sustained increase in locomotion, which facilitates food localization and acquisition and hence composes an important aspect of food-seeking behavior. This study investigated how nutritional states modulate starvation-induced hyperactivity in adult Drosophila. The receptor of adipokinetic hormone (AKHR), the insect analog of glucagon, is required for starvation-induced hyperactivity. AKHR is expressed in a small group of octopaminergic neurons in the brain. Silencing AKHR+ neurons and blocking octopamine signaling in these neurons eliminates starvation-induced hyperactivity, whereas activation of these neurons accelerates the onset of hyperactivity upon starvation. Neither AKHR nor AKHR+ neurons are involved in increased food consumption upon starvation, suggesting that starvation-induced hyperactivity and food consumption are independently regulated. Single cell analysis of AKHR+ neurons identified the co-expression of Drosophila insulin-like receptor (dInR), which imposes suppressive effect on starvation-induced hyperactivity. Therefore, insulin and glucagon signaling exert opposite effects on starvation-induced hyperactivity via a common neural target in Drosophila.

Wei, Y., Gokhale, R. H., Sonnenschein, A., Montgomery, K. M., Ingersoll, A. and Arnosti, D. N. (2016). Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator. Development 143: 3591-3603. PubMed ID: 27702787
Insulin signaling plays key roles in development, growth and metabolism through dynamic control of glucose uptake, global protein translation and transcriptional regulation. Altered levels of insulin signaling are known to play key roles in development and disease, yet the molecular basis of such differential signaling remains obscure. Expression of the insulin receptor (InR) gene itself appears to play an important role, but the nature of the molecular wiring controlling InR transcription has not been elucidated. This study characterized the regulatory elements driving Drosophila InR expression and found that the generally broad expression of this gene is belied by complex individual switch elements, the dynamic regulation of which reflects direct and indirect contributions of FOXO, EcR, Rbf and additional transcription factors through redundant elements dispersed throughout approximately 40 kb of non-coding regions. The control of InR transcription in response to nutritional and tissue-specific inputs represents an integration of multiple cis-regulatory elements, the structure and function of which may have been sculpted by evolutionary selection to provide a highly tailored set of signaling responses on developmental and tissue-specific levels.
Tanabe, K., Itoh, M. and Tonoki, A. (2017). Age-related changes in Insulin-like signaling lead to intermediate-term memory impairment in Drosophila. Cell Rep 18: 1598-1605. PubMed ID: 28199832
Insulin and insulin-growth-factor-like signaling (IIS) plays important roles in the regulation of development, growth, metabolic homeostasis, and aging, as well as in brain functions such as learning and memory. The temporal-spatial role of IIS in learning and memory and its effect on age-dependent memory impairment remain unclear. This study reports that intermediate-term memory (ITM), but not short-term memory (STM), in Drosophila aversive olfactory memory requires transient IIS during adulthood. The expression of Drosophila insulin-like peptide 3 (Dilp3) in insulin-producing cells and insulin receptor function in the fat body are essential for ITM. Although the expression of dilp3 decreases with aging, which is unique among dilp genes, the transient expression of dilp3 in aged flies enhances ITM. These findings indicate that ITM is systemically regulated by communication between insulin-producing cells and fat body and that age-dependent changes in IIS contribute to age-related memory impairment.

Lebreton, S., Carlsson, M. A. and Witzgall, P. (2017). Insulin signaling in the peripheral and central nervous system regulates female sexual receptivity during starvation in Drosophila. Front Physiol 8: 685. PubMed ID: 28943854
Many animals adjust their reproductive behavior according to nutritional state and food availability. Drosophila females for instance decrease their sexual receptivity following starvation. Insulin signaling, which regulates many aspects of insect physiology and behavior, also affects reproduction in females. This study shows that insulin signaling is involved in the starvation-induced reduction in female receptivity. More specifically, females mutant for the insulin-like peptide 5 (dilp5) were less affected by starvation compared to the other dilp mutants and wild-type flies. Knocking-down the insulin receptor, either in all fruitless-positive neurons or a subset of these neurons dedicated to the perception of a male aphrodisiac pheromone, decreased the effect of starvation on female receptivity. Disrupting insulin signaling in some parts of the brain, including the mushroom bodies even abolished the effect of starvation. In addition, fruitless-positive neurons in the dorso-lateral protocerebrum and in the mushroom bodies co-expressing the insulin receptor were identified. Together, these results suggest that the interaction of insulin peptides determines the tuning of female sexual behavior, either by acting on pheromone perception or directly in the central nervous system.

Each individual organ grows by controlling cell number and/or cell size to reach its final dimensions in relation to the size of the organism. This process is tightly regulated and modulated by environmental factors such as nutrient availability and temperature. How organ growth is coordinated within a single individual is still poorly understood. In mammals, hormones and growth factors are known to play a predominant role in controlling organismal growth by orchestrating cell growth, cell proliferation, and cell survival. Reducing the levels of growth hormone or its mediators, insulin like growth factor (IGF1) and the IGF1 receptor (IGF1R), strongly affects body and organ size. In contrast to the well-established role of the IGF1R in growth control, a corresponding role of the insulin receptor is less well understood (Brogiolo, 2001 and references therein).

Genetic studies in Drosophila have highlighted an evolutionarily conserved signaling pathway that plays an essential role in controlling body, organ, and cell size. This pathway involves the homolog of the insulin receptor substrates (Chico), Phosphotidylinositol 3 kinase (Dp110), Pten, Akt/PKB, and RPS6-p70-protein kinase (S6K). Mutations in any one of these components lead to a change in cell size and, with the exception of S6K, in cell number as well. Conversely, overexpression of Dp110 or Akt1 leads to an increased cell size without affecting cell numbers. Thus, it appears that stimulation of the PI(3)K/PKB pathway alone is not sufficient to promote cell growth and cell cycle progression (Brogiolo, 2001 and references therein).

It is not known, however, whether the effect of InR on growth is cell autonomous and whether activation of InR is sufficient to promote growth and cell division. Furthermore, the identity of a ligand(s) for InR has remained elusive. It is now clear, however, that there are seven insulin-like genes in Drosophila and that these are expressed in a highly tissue- and stage-specific pattern. InR regulates organ size by changing cell size and cell number in a cell-autonomous manner. An amino acid substitution at the corresponding position in the kinase domain of the human and Drosophila insulin receptors causes severe growth retardation. Overexpression of one of the insulin-like genes alters growth control in an InR-dependent manner. With the discovery of the ligands for InR, research on the insulin receptor pathway function enters a new phase of clarity and biological interest (Brogiolo, 2001 and references therein).

The Drosophila homolog of the insulin/IGF1 receptor, InR, is essential for normal development and is required for the formation of the epidermis and the central and peripheral nervous systems during embryogenesis (Fernandez, 1995). All described alleles of InR are recessive embryonic or early larval lethal. Only weak heteroallelic combinations of InR alleles were found to be viable and yield adults with a severe developmental delay, small body size, and female sterility (Fernandez, 1995, Chen, 1996 and Brogiolo, 2001).

Flies that are homozygous for a partial loss-of-function mutation in InR (InRE19) (Chen, 1996) show a phenotype similar to that previously described for weak heteroallelic combinations. The developmental time is extended from 10 to 20 days, and body size is severely but proportionally reduced. The mutant flies are approximately half the weight of their heterozygous siblings, and females are sterile. Furthermore, like chico mutant flies, InRE19 flies have an almost 2-fold increase in lipid content. The small body size is attributable to a reduction in cell size and cell number by 23% and 17%, respectively as revealed by measuring cell density in the wing. Similarly, the average number of ommatidia in the compound eye of mutant male flies is 378 +/- 8 compared to 683 +/- 8 in heterozygous control flies. No dominant size reduction was observed with various InR alleles (Brogiolo, 2001).

The reduced overall size could be due to InR acting in the humoral regulation of growth or to it functioning autonomously in a cell- and tissue-specific manner. To test whether InR affects body parts autonomously, InR function in the eye imaginal disc was selectively removed using the ey-FLP technique. The eye imaginal disc gives rise to the adult eye and the head capsule. Mosaic flies with heads largely homozygous for various InR alleles display a dramatic reduction in eye tissue and in the head capsule, whereas the other body parts are of wild-type size. Notably, the head size is dependent on the allele. This allowed alleles to be arranged according to their phenotypic strength. The strongest reduction in head size was observed with InR339, a putative null allele, followed by InR31, InR211, InRE19, and InR353. Thus, InR regulates head size autonomously (Brogiolo, 2001).

A comparison of homozygous mutant tissue with heterozygous tissue in tangential sections of mosaic eyes reveals an estimated reduction in ommatidial size of one third for InRE19 homozygous mutant tissue and of more than half for a candidate null allele. Importantly, this growth defect does not impede proper cell fate determination, given that the normal arrangement of the photoreceptor rhabdomeres is retained. Furthermore, the cell size reduction is cell autonomous, as can be seen at the border between homozygous mutant tissue and heterozygous tissue; within the same ommatidial unit, small homozygous cells coexist with normal-sized heterozygous cells. Although cells lacking InR function survive and differentiate normally, they have a growth disadvantage compared to heterozygous cells. When homozygous mutant cell clones are induced during early larval life and analyzed in the imaginal discs in the third instar, clone size is greatly reduced, compared to the wild-type sister clone. The phenotypes of InR mutant cells are strikingly similar to those of mutants in the Pi(3)K/PKB pathway. Therefore, it is likely that InR directly regulates cell growth at least in part through the Pi(3)K/PKB pathway (Brogiolo, 2001).

The structure of InR is similar to the mammalian insulin receptor (Inr) and the IGF1 receptor (IGF1R). It is a tetramer composed of two subunits containing the putative ligand binding domains and two transmembrane subunits containing the cytoplasmic tyrosine kinase domains. In contrast to human receptors, InR possesses extensions at the amino and carboxy termini. The C-terminal extension contains binding sites for downstream components similar to those found in insulin receptor substrates (IRS), and has been shown to be able to signal in the absence of IRS proteins (Yenush, 1996). Furthermore, genetic evidence in Drosophila suggests that InR can signal in the absence of Chico, the IRS1-4 homolog. In order to understand the molecular basis for differences in strength of InR phenotypes, the cytoplasmic region of several InR alleles was sequenced. In the cytoplasmic portion, 5 out of 22 alleles carry a point mutation. All of them map to conserved amino acid residues within the kinase domain. Two of these point mutations lead to premature stop codons and three are missense mutations. In humans, most of the mutations that occur within the tyrosine kinase domain of the Inr have been shown to impair insulin-stimulated tyrosine kinase activity. InR353 (Arg1419Cys) affects an active site residue, which mediates insulin receptor kinase substrate specificity. Remarkably, a human patient with severe growth retardation associated with insulin resistance, a syndrome called leprechaunism, carries an amino acid exchange at the corresponding position (Arg1092Glu). It is the only reported homozygous viable mutation in the kinase domain of the human Inr. The patient's parents were heterozygous for this substitution and had severe insulin resistance, but no growth anomalies. Similarly, heterozygosity for InR alleles does not lead to growth phenotypes. These results suggest a role for the insulin receptor in growth control that has been conserved from insects to humans (Brogiolo, 2001).

It has been proposed that a bona fide growth control gene should meet two criteria, namely that elimination should result in growth retardation, whereas overexpression of the gene should promote excessive growth. To determine whether InR has a direct growth- and proliferation-promoting effect, a wild-type InR cDNA was overexpressed using the UAS/Gal4 system. Expressing UAS-InRwt specifically in proliferating eye precursor cells using an eyeless-Gal4 driver results in a dramatic outgrowth in the adult eye because of an increase in the number of ommatidia. Histological sections through the overgrown eyes reveal essentially normal cell differentiation but a slight increase in the size of photoreceptor cell bodies. To further explore the effect on cell size, InR was overexpressed in clones of cells during cell differentiation. External observation of such clones shows strongly enlarged ommatidia. Histological sections reveal a cell-autonomous increase in photoreceptor cell size but only a moderate disruption of the ommatidial pattern. Taken together, these results indicate that InR activity controls growth in two ways: by regulating both cell proliferation and cell size. Interestingly, although overexpression of Dp110 has been shown to increase cell size, it does not increase cell division rates. The IRS homolog Chico contains consensus binding sites for the Drk/Grb2 adaptor and thus may provide a link to the Ras/MAPK pathway. Activation of InR may promote cell growth and cell division by activation of two signaling pathways. Indeed, MAPK activation is observed in extracts of heads overexpressing an activated form of InR (Brogiolo, 2001).

To identify extracellular ligands that regulate InR activity during development, a search of the Drosophila genome was carried out, looking for genes encoding insulin-like peptides. Using the conserved spacing of four cysteines within the A chain as a signature for insulin-like peptides, seven predicted genes matching these criteria were identified, and termed dilp1-7, for Drosophila insulin-like peptides (DILP). dilp1-5 are on the third chromosome at cytological position 67C1-2, and constitute a cluster of four contiguous insulin-related genes, with dilp5 separated by one intervening gene from dilp4. The other genes, dilp6 and dilp7, are on the X chromosome at two different loci at cytological positions 2F4 and 3F2, respectively. dilp1-7 encode putative precursor proteins of 107 to 156 amino acid residues in length that are structurally similar to preproinsulin, with a signal peptide, a B chain, a C peptide, and an A chain. Consensus cleavage sites between the B and A chains of all seven DILPs suggest that the active peptides consist of two separate polypeptide chains. Thus, these peptides resemble insulin rather than IGF1 or IGF2, which are single polypeptides. Comparison of the amino acid sequence of the A and B chains of DILP1-7 with insulin, IGF1, and IGF2 again reveals a higher degree of identical amino acids between these peptides and insulin. DILP2 is the most closely related, with 35% identity to mature insulin. These structural similarities suggest that DILP1-7 are candidate ligands for InR (Brogiolo, 2001).

To determine the expression pattern of the insulin-like genes, in situ hybridization was performed on embryos and larval tissues. In the embryo, only dilp2, dilp4, and dilp7 are expressed at different levels in the mesoderm and midgut. It is interesting to note that the main insulin-producing organs in mammals, the Langerhans islets in the pancreas, are of endodermal origin. Four of the seven genes show a remarkably specific and unique pattern of expression in larvae. dilp2, dilp3, and dilp5 display high expression levels in seven cells of anteromedial localization in the brain hemispheres that may correspond to neurosecretory cells. dilp3 is exclusively transcribed in these seven cells during larval development, whereas dilp2 and dilp5 show additional expression domains. dilp7 mRNA detection is restricted to the ventral nerve cord in a segmental fashion; in four pairs of ventrally located cells in the most posterior abdominal segments, and in one pair of dorsally located cells in A1 or A2. Interestingly, none of the dilps shows detectable levels of expression in the larval fat body (Brogiolo, 2001).

Expression of insulin-related genes in neurosecretory cells has been identified in other invertebrates, such as the insects Bombyx mori and Locusta migratoria and in the mollusc Lymnaea stagnalis (Kawakami, 1989, Hetru, 1991 and Smit, 1988). In Bombyx mori, the neurosecretory cells in the brain are connected to the corpora cardiaca, a secretory gland from which release of insulin-like hormones is triggered by nutrient levels (possibly carbohydrate levels) (Masumura, 2000). It is speculated that DILP-expressing neurosecretory cells are connected to the ring gland (the compound endocrine gland of Drosophila), which includes the cells of the corpora cardiaca. Release of DILPs from the ring gland may also be under nutritional control. The complex expression pattern of the DILPs, however, suggests a combination of neurosecretory and autocrine/paracrine control mechanisms of cell growth and division during larval development. Mutations in individual dilp genes or targeted ablation of specific DILP-expressing cells may help resolve the functions of the Drosophila insulins (Brogiolo, 2001).

To gain insight into the function of the DILPs, one insulin-like peptide was overexpressed. For this purpose, DILP2 was chosen, because it is the closest homolog of human insulin and because it is the only DILP with broad expression in imaginal discs. If DILP2 is a limiting ligand of InR, it would be expected that overexpression of DILP2 should promote growth. Indeed, repeated induction of ubiquitous expression of DILP2 during development by means of the UAS/Gal4 system gives rise to bigger flies (39% increase in body weight). Analysis of the eyes of such flies reveals an increase in the number of ommatidia (from 733+/-10 to 767+/-25 in male flies). Furthermore, quantitative analysis of the wing blade shows an increase in both cell size (by 9%) and cell number (by 11%). These results suggest a role for DILP2 in controlling organism size by augmenting both the cell number and cell size of different organs (Brogiolo, 2001).

In humans, the in vivo role of insulin as a growth factor is inferred from clinical syndromes, in which excessive insulin secretion results in excessive growth and where a severe deficiency of insulin secretion is associated with poor intrauterine and postnatal growth. For instance, neonates born to women with diabetes in pregnancy or born with Beckwith-Wiedemann syndrome or Nesidioblastosis are macrosomic. In all cases, the growth anomaly is associated with hyperinsulinemia during embryonic development. The demonstration in transgenic flies that overexpression of an insulin-like peptide during development can increase animal size provides further evidence for an evolutionarily conserved role of the insulin pathway in growth control (Brogiolo, 2001).

The complementarity between the loss-of-function phenotype of InR and the DILP2 overexpression phenotype (increase in size) suggests that DILP2 may be one of the ligands for InR. A deficiency [Df(3L)AC1] uncovering dilp1-5 was found to dominantly suppressed the big and rough eye phenotype caused by targeted overexpression of InR in differentiating eye cells. To test whether the observed dominant suppression is caused by hemizygosity for dilp2, the dilp2 gene dosage was selectively increased by crossing in the UAS-dilp2 transgene. A single copy of UAS-dilp2 is sufficient to revert the suppression by Df(3L)AC1, strongly suggesting that dilp2 is rate limiting for the InR overexpression phenotype. An analysis of individually mutated dilp genes will be required to determine the contribution of the other dilps of the cluster (dilp13-5) to the suppressive effect of Df(3L)AC1 (Brogiolo, 2001).

To examine whether InR is limiting for the DILP2 overexpression phenotype, InR activity was lowered in a DILP2-overexpressing background. Indeed, introducing one mutant copy of InR (InR304) dominantly reduces the increased body weight, cell size, and cell number caused by ubiquitous DILP2 overexpression, indicating a strong genetic interaction between InR and dilp2. Persistent expression of DILP2 under the control of an actin promoter (Act5C-Gal4) causes embryonic lethality. This lethality is dependent on normal levels of InR, since expression of DILP2 in the presence of strongly reduced levels of InR generate viable adults that are small and developmentally delayed. These results are consistent with InR mediating the effects of DILP2. Furthermore, given that a viable heteroallelic combination of PKB alleles is also able to suppress the embryonic lethal phenotype of DILP2 overexpression, it is postulated that the action of DILP2 by InR is transduced at least in part through the Chico/Pi(3)K/PKB pathway (Brogiolo, 2001).

In humans, syndromes with mutations in the insulin receptor or with excessive insulin secretion lead to growth abnormalities. This study shows in vivo that altering expression levels of a Drosophila insulin-like gene and varying the activity of the Drosophila insulin receptor changes the size and number of cells in organs, thereby regulating organism size. It seems, therefore, that the insulin receptor pathway has been conserved during evolution for a role in growth control from insects to humans. Given the highly tissue-specific expression of the dilps in the central nervous system and a broad expression in precursor tissues of adult organs, a nutritionally regulated mechanism is proposed whereby Drosophila insulin-like peptides coordinate growth in a neurosecretory and local fashion (Brogiolo, 2001).


Amino Acids - 2146

Structural Domains

A Drosophila genomic fragment has been isolated with a deduced amino acid sequence that is strikingly homologous to that of the kinase domain of the human insulin receptor. The Drosophila DNA hybridizes with an 11-kilobase mRNA that is most prominent in 8- to 12-hr embryos. An anti-peptide antibody prepared to a sequence in the human insulin receptor kinase domain that is conserved in the Drosophila sequence immunoprecipitates a single 95-kDa Drosophila protein whose phosphorylation on tyrosine residues is dependent on insulin. It is concluded that the DNA sequence is that of the kinase domain of the Drosophila insulin receptor and that the 95-kDa phosphoprotein is the autophosphorylated beta subunit of that receptor. The results are compatible with reports demonstrating a specific insulin-binding Drosophila glycoprotein and an insulin-dependent tyrosine protein kinase whose activity is greatest during embryogenesis. The observations suggest a role for insulin-dependent protein tyrosine phosphorylation during embryogenesis (Petruzzelli, 1986).

The cloning and primary structure of the Drosophila insulin receptor gene (InR) is reported, along with functional expression of the predicted polypeptide, and the isolation of mutations in the InR locus. The structure and processing of the Drosophila insulin proreceptor are somewhat different from those of the mammalian insulin and IGF 1 receptor precursors. The InR proreceptor [M(r) 280 kDa] is processed proteolytically to generate an insulin-binding alpha subunit [M(r) 120 kDa] and a beta subunit [M(r) 170 kDa] with protein tyrosine kinase domain. The InR beta 170 subunit contains a novel domain at the carboxyterminal side of the tyrosine kinase, in the form of a 60 kDa extension that contains multiple potential tyrosine autophosphorylation sites. This 60 kDa C-terminal domain undergoes cell-specific proteolytic cleavage that leads to the generation of a total of four polypeptides (alpha 120, beta 170, beta 90, and a free 60 kDa C-terminus) from the inr gene. These subunits assemble into mature InR receptors with the structures alpha 2(beta 170)2 or alpha 2(beta 90)2 (Fernandez, 1995).

The nucleic acid and deduced amino acid sequence of the Drosophila insulin receptor homolog (InR) has been determined. The coding sequence of InR is contained within 10 exons spanning less than 8 kilobase pairs of genomic DNA. The deduced amino acid sequence of the dir encodes a protein of 2148 amino acids, larger than the human insulin receptor due to amino- and carboxyl-terminal extensions. The overall level of amino acid identity between the InR and human insulin and insulin-like growth factor-I receptors is 32.5% and 33.3%, respectively. Higher levels of identity are found in exon 2 (45% and 43%, respectively) and in the beta subunit (50% and 48%, respectively), and the positions of most cysteine residues in the alpha subunit cysteine-rich domain are conserved. A novel, 400-amino acid, carboxyl-terminal extension contains 9 tyrosine residues, four of which are present in YXXM or YXXL motifs, suggesting that they function as binding sites for SH2 domain-containing signaling proteins. The presence of multiple putative SH2 domain binding sites in the InR represents a significant difference from its mammalian homologs and suggests that, unlike the human insulin and insulin-like growth factor-I receptors, the InR forms stable complexes with signaling molecules as part of its signal transduction mechanism (Ruan, 1995).

A Drosophila cDNA clone was obtained using the human insulin receptor cDNA sequence as a probe. The 3586 bp nucleotide sequence predicted a single polypeptide of 1095 amino acid residues, which showed considerable homology (35.2%) with the human insulin receptor precursor. Although the cDNA was incomplete at its 5'-terminal region, it encodes a transmembrane glycoprotein as a single precursor of a two subunit molecule having a structural architecture similar to that of the human insulin receptor precursor. The presumptive beta subunit carries a well conserved Tyr kinase domain which showed 63.5% homology with that of human insulin receptor (Nishida, 1986).

Insulin-like receptor : Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

date revised: 10 March 2001

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