Project: Research project

Project Details


The insulin-like growth factors (IGFs) are 7.5kD peptides, structurally
homologous to insulin, which mediate many of the anabolic effects of
growth hormone in vivo, and are mitogenic for a variety of cell types in
vitro. Importantly, plasma and other biological fluids contain multiple
proteins that specifically bind IGFs. These IGF binding proteins have
distinct molecular sizes, biochemical characteristics, and immunological
determinants, and may be pivotal in directing and modulating IGF action
at the cellular level Three IGF binding proteins have been cloned and
sequenced, but others have been detected and have yet to be
characterized. The precise interactions among the various IGF binding
proteins and IGF peptides, and the regulatory mechanisms for IGF binding
protein production are largely unknown.
Our central hypothesis is that the IGF binding proteins are
integral components of IGF physiology that define and coordinate IGF and
insulin action at the level of the target cell We propose that the
production of IGF binding proteins in their multiple discrete forms are
under specific hormonal control, and that the different IGF binding
proteins have distinct biological functions in modulating IGF action. A
unique feature of this proposal is the planned, stepwise integration of
mechanistic experiments using both in vitro and clinical models. The
specific aims of this research project are (1) to develop and carefully
characterize in vitro models appropriate for the study of IGF binding
proteins, (2) to determine the transcriptional and translational control
of IGF binding protein synthesis under defined conditions, and assess
qualitative and quantitative changes in IGF binding protein production
peculiar to cell type and during development, aging, and transformation,
(3) to ascertain the mechanism of action of purified IGF binding
proteins, and (4) to define the regulation of IGF binding proteins in
vivo since the physiological actions of IGFs are, in part, regulated by
the availability and type of binding protein to which the peptide is
The principal investigator has expertise in the various
techniques of biochemistry, molecular biology, and cellular physiology
necessary for the success of this proposal. These studies will help
clarify the integrated role of IGFs and IGF binding proteins in the
control of cell growth, and provide important insight into the biological
consequences of altered IGF binding protein production and, therefore,
IGF action in various physiological and pathophysiological states.
StatusNot started


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