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PMID: 8246974 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hematopoietic cell phosphatase associates with the interleukin-3 (IL-3) receptor beta chain and down-regulates IL-3-induced tyrosine phosphorylation and mitogenesis.

Molecular and cellular biology ·Vol. 13 ·No. 12 ·1993-12-00 ·Pages 7577-86

Yi T, Mui AL, Krystal G, Ihle JN

Abstract

Hematopoietic cell phosphatase (HCP) is a tyrosine phosphatase with two Src homology 2 (SH2) domains that is predominantly expressed in hematopoietic cells, including cells whose growth is regulated by interleukin-3 (IL-3). The potential effects of HCP on IL-3-induced protein tyrosine phosphorylation and growth regulation were examined to assess the role of HCP in hematopoiesis. Our studies demonstrate that, following ligand binding, HCP specifically associates with the beta chain of the IL-3 receptor through the amino-terminal SH2 domain of HCP, both in vivo and in vitro, and can dephosphorylate the receptor chain in vitro. The effects of increasing or decreasing HCP levels in IL-3-dependent cells were assessed with dexamethasone-inducible constructs containing an HCP cDNA in sense and antisense orientations. Increased HCP levels were found to reduce the levels of IL-3-induced tyrosine phosphorylation of the receptor and to dramatically suppress cell growth. Conversely, decreasing the levels of HCP increased IL-3-induced tyrosine phosphorylation of the receptor and marginally increased growth rate. These results support a role for HCP in the regulation of hematopoietic cell growth and begin to provide a mechanistic explanation for the dramatic effects that the genetic loss of HCP, which occurs in motheaten (me) and viable motheaten (mev) mice, has on hematopoiesis.

MeSH Terms
Animals Cell Division/drug effects Cell Line Down-Regulation Hematopoiesis/drug effects,genetics,physiology Hematopoietic Stem Cells/drug effects,metabolism Interleukin-3/pharmacology Intracellular Signaling Peptides and Proteins Mice Mice, Mutant Strains Phosphorylation Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases/genetics,metabolism Receptors, Interleukin-3/metabolism Transfection Tyrosine/metabolism
Chemicals
Interleukin-3 Intracellular Signaling Peptides and Proteins Receptors, Interleukin-3 Tyrosine Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases Ptpn6 protein, mouse
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yi T
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Mui A L
Krystal G
Ihle J N
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.12.7577-7586.1993
Published
1993-12-00
Pages
7577-86
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364829
Subset
IM
Grants
NCI NIH HHS · P30 CA21765 · United States
NIDDK NIH HHS · R01 DK42932 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.12.7577-7586.1993 PMC Full Text View journal details
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