The Drosophila insulin receptor is required for normal growth
Chi Chen,J Jack,R S Garofalo +2 more
TLDR
Interestingly, the severity of the mutant phenotype correlates with biochemical measures of loss of function of the receptor tyrosine kinase, suggesting a conserved function for this growth factor family in the regulation of growth and body size.Abstract:
Drosophila contain an insulin receptor homologue, encoded by the inr gene located at position 93E4-5 on the third chromosome. The receptor protein is strikingly homologous to the human receptor, exhibiting the same alpha2beta2 subunit structure and containing a ligand- activated tyrosine kinase in its cytoplasmic domain. Chemical mutagenesis was used to induce mutations in the inr gene and six independent mutations that lead to a loss of expression or function of the receptor protein were identified. These mutations are recessive, embryonic, or early larval lethals, but some alleles exhibit heteroallelic complementation to yield adults with a severe developmental delay (10 days), growth-deficiency, female-sterile phenotype. Interestingly, the severity of the mutant phenotype correlates with biochemical measures of loss of function of the receptor tyrosine kinase. The growth deficiency appears to be due to a reduction in cell number, suggesting a role for inr in regulation of cell proliferation during development. The phenotype is reminiscent of those seen in syndromes of insulin-resistance or IGF-I and IGF-I receptor deficiencies in higher organisms, suggesting a conserved function for this growth factor family in the regulation of growth and body size.read more
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The PI3K-PDK1 connection: more than just a road to PKB.
TL;DR: The mechanism by which PKB is activated and the downstream actions of this multifunctional kinase are reviewed, as well as the evidence that PDK1 may be involved in the activation of protein kinases other than PKB, and the possibility that some of the currently postulated PKB substrates targets might in fact be phosphorylated byPDK1-regulated kinasesother than P KB.
Journal ArticleDOI
Synthesis and Function of 3-Phosphorylated Inositol Lipids
Bart Vanhaesebroeck,Sally J. Leevers,Khatereh Ahmadi,John F. Timms,Roy Katso,Paul C. Driscoll,Rudiger Woscholski,Peter J. Parker,Michael D. Waterfield +8 more
TL;DR: This review is focused on the 3-phosphoinositide lipids, the synthesis of which is acutely triggered by extracellular stimuli, the enzymes responsible for their synthesis and metabolism, and their cell biological roles.
Journal ArticleDOI
A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function.
TL;DR: It is concluded that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue.
Journal ArticleDOI
Extension of Life-Span by Loss of CHICO, a Drosophila Insulin Receptor Substrate Protein
David J. Clancy,David Gems,Lawrence G. Harshman,Sean Oldham,Hugo Stocker,Ernst Hafen,Sally J. Leevers,Linda Partridge +7 more
TL;DR: It is found that mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes, and the role of insulin/IGF signaling in regulating animal aging is evolutionarily conserved.
Journal ArticleDOI
An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control
TL;DR: This study shows that the Drosophila insulin receptor autonomously controls cell and organ size, and that overexpression of a gene encoding an insulin-like peptide is sufficient to increase body size.
References
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Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)
Jeh-Ping Liu,Julie C. Baker,Archlbald S. Perkins,Elizabeth J. Robertson,Argiris Efstratiadis +4 more
TL;DR: In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis.
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Role of Insulin-like Growth Factors in Embryonic and Postnatal Growth
TL;DR: Postnatal growth curves indicated that surviving Igf-1(-/-) mutants, which are infertile and exhibit delayed bone development, continue to grow with a retarded rate after birth in comparison with wild-type littermates and become 30% of normal weight as adults.
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