BIOMAT Database Logo BIOMAT Database Logo

Insulin and insulin-like growth factors stimulate in vivo receptor autophosphorylation and tyrosine phosphorylation of a 70K substrate in cultured fetal chick neurons. 1991

K A Kenner, and K A Heidenreich
Department of Medicine, University of California, San Diego, La Jolla 92093.

Insulin and insulin-like growth factors (IGFs) have been shown to regulate neuronal growth and differentiation. To investigate the possible role of tyrosine phosphorylation in the neurotrophic actions of these peptides, we examined the effects of insulin, IGF-I, and IGF-II on tyrosine phosphorylation in cultured fetal chick neurons. Tyrosine phosphorylation was detected by immunoblot analysis using antiphosphotyrosine antibodies. Under basal conditions five major phosphoproteins (170K, 140K, 115K, 103K, and 44K) and a number of minor proteins were detected by three separate antisera. In response to insulin, IGF-I, or IGF-II, an 87K membrane-associated protein (pp87) became phosphorylated on tyrosine in a rapid, dose-dependent manner. The Mr of pp87 was identical to that of the insulin and IGF-I receptor beta-subunits. Comparison of the dose-response curves for pp87 phosphorylation by insulin and IGF-I suggests that each peptide stimulated autophosphorylation of its own receptor beta-subunit. The maximal response obtained with IGF-I was approximately 10-fold higher than that obtained with insulin (3- to 5-fold), consistent with the larger number of IGF-I receptors in these cells. The maximal response obtained with IGF-II was 4- to 7-fold higher than that with insulin, suggesting that it acts through the insulin receptor as well. Tyrosine that IGF-II acts through the insulin receptor as well. Tyrosine phosphorylation of other proteins by the activated receptor kinases was not detected in neurons cultured for 5 days, however neurons cultured for only several h contained a predominant 70K protein (pp70) that was phosphorylated on tyrosine in response to all three hormones. Tyrosine phosphorylation of pp70 was maximal after 2-5 h in culture and was undetectable in neurons cultured longer than 24 h. The time course and dose dependence of pp70 phosphorylation in response to hormone paralleled that of insulin and IGF-I receptor autophosphorylation. These results demonstrate that both insulin and IGF-I receptors are active tyrosine kinases in fetal neurons, and that pp70 represents a potential endogenous substrate for the insulin and IGF-I receptor kinases. The transient phosphorylation of pp70 may be involved in the neurotrophic effects of insulin and insulin-like growth factors.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D007335 Insulin-Like Growth Factor II A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults. IGF-II,Multiplication-Stimulating Activity,Somatomedin MSA,IGF-2,Insulin Like Growth Factor II,Insulin-Like Somatomedin Peptide II,Multiplication-Stimulating Factor,Somatomedin A,Factor, Multiplication-Stimulating,Insulin Like Somatomedin Peptide II,Multiplication Stimulating Activity,Multiplication Stimulating Factor
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010750 Phosphoproteins Phosphoprotein
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D011972 Receptor, Insulin A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE. Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors

Related Publications

K A Kenner, and K A Heidenreich
Insulin and metabolic stress stimulate multisite serine/threonine phosphorylation of insulin receptor substrate 1 and inhibit tyrosine phosphorylation.
May 2014, The Journal of biological chemistry,
K A Kenner, and K A Heidenreich
Growth factors and insulin stimulate tyrosine phosphorylation of the 51C/SHIP2 protein.
July 1998, The Journal of biological chemistry,
K A Kenner, and K A Heidenreich
Growth hormone stimulates tyrosine phosphorylation of insulin receptor substrate-1.
December 1994, The Journal of biological chemistry,
K A Kenner, and K A Heidenreich
Insulin-like growth factors and insulin stimulate erythropoietin production in primary cultured astrocytes.
January 1997, Brain research,
K A Kenner, and K A Heidenreich
Estradiol stimulates tyrosine phosphorylation of the insulin-like growth factor-1 receptor and insulin receptor substrate-1 in the uterus.
October 1996, Proceedings of the National Academy of Sciences of the United States of America,
K A Kenner, and K A Heidenreich
Phosphorylation of insulin-like growth factor I receptor by insulin receptor tyrosine kinase in intact cultured skeletal muscle cells.
May 1988, Biochemistry,
K A Kenner, and K A Heidenreich
[Phosphorylation of the receptor insulin and insulin-like growth factors].
March 1985, Gan to kagaku ryoho. Cancer & chemotherapy,
K A Kenner, and K A Heidenreich
Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons.
August 1997, The Journal of biological chemistry,
K A Kenner, and K A Heidenreich
Protein phosphatase-1 and -2a activities in cultured fetal chick neurons: differential regulation by insulin and insulin-like growth factor-I.
November 1993, Endocrinology,
K A Kenner, and K A Heidenreich
Insulin-like growth factors stimulate synthesis of nucleic acids and glycogen in cultured calvaria cells.
July 1983, Calcified tissue international,
Copied contents to your clipboard!