INSULIN-LIKE GROWTH FACTORS AND MUSCLE DIFFERENTIATION

  • Rotwein, Peter, (PI)

    Project: Research project

    Description

    Insulin-like growth factors I and II exert pleiotropic effects on diverse
    cell types. Although current evidence supports a role for IGF-I as a major
    postnatal growth factor, regulated in part by growth hormone, the functions
    of IGF-II in growth and development remain undefined. Each IGF interacts
    initially with a unique high-affinity receptor located in the plasma
    membrane of responsive cells. Many of the actions of both peptides are
    mediated by the IGF-I receptor, a ligand-activated tyrosine-specific
    protein kinase structurally related to the insulin receptor. By contrast
    the role of the IGF-II receptor in IGF signaling is unclear, despite its
    apparent identity with the cation-independent mannose-6phosphate receptor
    involved in targeting lysosomal enzymes. As an additional complexity
    actions of both IGFs in target tissues may be modified by interaction with
    various locally-secreted binding proteins. As part of a long-term goal to
    define the mechanisms by which the actions of the IGFs are integrated
    within the cell, the focus of this application will be on the functions and
    regulation of IGF-II, the IGF-II receptor, and a novel IGF binding protein
    in a model cell system, the differentiating myoblast. Toward this end the
    following four specific aims are proposed: 1.To determine the role of IGF-II in muscle differentiation and to define
    its mechanisms of qlction. 2.To dissect the functions of the IGF-II gene promoter, in order to define
    and characterize the elements required for induction of gene expression
    during myoblast differentiation. 3.To define the function of the IGF-II receptor in muscle differentiation
    and to characterize the mechanisms involved in regulation of receptor gene
    expression in this model system. 4.To determine the mechanisms of action and the regulation of a novel IGF
    binding protein whose secretion is induced during myoblast differentiation.
    StatusFinished
    Effective start/end date1/1/911/31/18

    Funding

    • National Institutes of Health: $244,928.00
    • National Institutes of Health: $143,528.00
    • National Institutes of Health: $276,679.00
    • National Institutes of Health: $15,000.00
    • National Institutes of Health: $255,684.00
    • National Institutes of Health
    • National Institutes of Health: $434,972.00
    • National Institutes of Health: $263,786.00
    • National Institutes of Health: $382,324.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $269,170.00
    • National Institutes of Health: $277,209.00
    • National Institutes of Health: $184,999.00
    • National Institutes of Health: $329,314.00
    • National Institutes of Health: $307,380.00
    • National Institutes of Health: $12,371.00
    • National Institutes of Health: $295,457.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $177,882.00
    • National Institutes of Health: $461,493.00
    • National Institutes of Health: $283,880.00
    • National Institutes of Health: $130,724.00
    • National Institutes of Health: $261,306.00
    • National Institutes of Health: $100,000.00
    • National Institutes of Health: $332,640.00
    • National Institutes of Health: $250,228.00

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    Somatomedins
    Insulin-Like Growth Factor II
    Muscles
    Myoblasts
    IGF Type 2 Receptor
    Muscle Development
    Insulin-Like Growth Factor Binding Protein 5
    IGF Type 1 Receptor
    Genes
    Carrier Proteins
    Insulin-Like Growth Factor I
    Insulin Receptor
    Transcription Factors
    Intercellular Signaling Peptides and Proteins
    Muscle Cells
    Protein-Tyrosine Kinases
    Embryonic Structures
    Insulin-Like Growth Factor Binding Proteins
    Fetus
    Growth Differentiation Factors

    ASJC

    • Medicine(all)