Abstract/Details

Characterization of the receptor protein tyrosine phosphatase gamma gene product


1998 1998

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Abstract (summary)

The PTPRG gene encodes a receptor tyrosine phosphatase protein with an estimated molecular weight of 185 kDa. Using a baculovirus overexpression system and a series of anti-peptide polyclonal antibodies generated in our laboratory, we examined the activity of the protein in vitro. PTP$\gamma$ was confirmed to be a tyrosine-specific phosphatase with distinct substrate specificities. A partially purified form of the enzyme was allosterically activated by triphosphorylated nucleosides. Ptp$\gamma$ was postulated to be involved in hematopoiesis since it is expressed exclusively in chick monoblast, erythroblast and lymphoblast cell lines but not in the respective mature precursors. Interestingly, Ptp$\gamma$ demonstrates a tightly regulated peak of expression during embryonic stem cell differentiation into embryoid bodies. We perturbed ES cell expression of Ptp$\gamma$ during differentiation in transfection experiments and examined the effect on hemaotpoietic colony formation in methyl cellulose. Stable clones overexpressing Ptp$\gamma$ were blocked during an early/intermediate stage of development. A significant reduction of the level of Ptp$\gamma$ expression in ES cells prohibited hematopoietic colony formation. This suggests that Ptp$\gamma$ is a permissive factor for an early event in hematopoietic differentiation but that its downregulation is required for the completion of the program. We investigated Ptp $\gamma$ expression during mouse embryogenesis using non-radioactive in situ hybridization procedures on whole and sectioned embryos. We observed a dynamic pattern of expression in many tissues throughout development and have suggested potential roles in limb morphogenesis, muscle development and commissural neuron migration and/or differentiation. We demonstrated overlapping or complimentary spatiotemporal patterns of expression of Ptp$\gamma$ and midkine in embryos and tested the hypothesis that midkine is a candidate ligand for Ptp$\gamma.$ Our in vitro experiments did not support a role for midkine as a Ptp$\gamma$ ligand.

Indexing (details)


Subject
Genetics;
Molecular biology
Classification
0369: Genetics
0307: Molecular biology
Identifier / keyword
Biological sciences, tyrosine phosphatase
Title
Characterization of the receptor protein tyrosine phosphatase gamma gene product
Author
Mendrola, Jeannine M.
Number of pages
177
Publication year
1998
Degree date
1998
School code
0272
Source
DAI-B 59/04, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780591817157, 0591817152
Advisor
Huebner, Kay
University/institution
Thomas Jefferson University
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
9829083
ProQuest document ID
304461086
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304461086
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