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Identification and Characterization of Glial Growth Factor

Citation

Lemke, Greg Erwin (1983) Identification and Characterization of Glial Growth Factor. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/774r-7520. https://resolver.caltech.edu/CaltechTHESIS:10182019-171906142

Abstract

A combination of biochemical, cell biological and immunological techniques have been employed to identify a novel and potent polypeptide mitogen of the brain and pituitary. This molecule, named glial growth factor (GGF), stimulates DNA synthesis and cell division in cultured rat Schwann cells, astrocytes, and fibroblasts.

Three independent lines of evidence indicate that GGF activity resides in a basic protein of molecular weight 3.1 x 104. (a) When partially purified preparations are analyzed by native gel electrophoresis at pH 4.5, mitogenic activity migrates with a protein of this molecular weight, as revealed by bioassay coupled with a second dimension of SDS gel electrophoresis. (b) A set of monoclonal antibodies which deplete growth factor activity from heterogeneous solutions specifically recognize a 31,000 dalton protein antigen, as determined by gel immunoautoradiography. (c) GGF activity is recovered at a molecular weight of 3.1 x 104 after denaturing polyacrylamide gel electrophoresis in SDS.

Three large-scale purifications of GGF, employing a combination of column chromatography steps and preparative electrophoreses, are described. The molecule has been purified to apparent homogeneity from anterior lobes of the bovine pituitary.

Through the use of nucleic acid precursor incorporation assays, GGF has been shown to be markedly mitogenic for rat Schwann cells, astrocytes and fibroblasts, but inactive when assayed on oligodendrocytes or microglia. Electrophoretic analyses suggest that all responsive cell types are stimulated by a single (the same) molecular species. GGF is the only defined mitogen to which rat Schwann cells respond.

Glial growth factor from bovine brain has been found to be indistinguishable from bovine pituitary GGF, as determined by biochemical, immunological and bioactivity criteria. GGF is non-uniformly distributed among bovine brain regions. It is present in brain extracts prepared from a wide variety of vertebrate species.

Purified human platelet-derived growth factor (PDGF) shares many important properties with GGF. PDGF has been shown to be unable to significantly stimulate the division of rat Schwann cells, however, and therefore appears to be distinct.

Observations made in vitro suggest several possible biological roles for GGF in vivo. These are discussed.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Biology
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Kennedy, Mary B. (advisor)
  • Brockes, Jeremy P. (co-advisor)
Thesis Committee:
  • Brockes, Jeremy P. (chair)
  • Hudspeth, A. James
  • Hood, Leroy E.
  • Revel, Jean-Paul
  • Kennedy, Mary B.
Defense Date:17 May 1983
Funders:
Funding AgencyGrant Number
United States Public Health Service (USPHS)UNSPECIFIED
Kroc FoundationUNSPECIFIED
Pew Memorial TrustUNSPECIFIED
CaltechUNSPECIFIED
Jean Weigle Memorial FundUNSPECIFIED
Record Number:CaltechTHESIS:10182019-171906142
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:10182019-171906142
DOI:10.7907/774r-7520
Related URLs:
URLURL TypeDescription
http://www.jbc.org/content/255/18/8374.shortPublisherArticle adapted for Chapter 1.
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11830
Collection:CaltechTHESIS
Deposited By: Melissa Ray
Deposited On:19 Oct 2019 00:57
Last Modified:16 Apr 2021 22:20

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