Growth Hormone Regulation of SIRP and SHP-2 Tyrosyl Phosphorylation and Association
Open Access
- 1 March 1998
- journal article
- Published by Elsevier BV
- Vol. 273 (12), 7112-7117
- https://doi.org/10.1074/jbc.273.12.7112
Abstract
SIRPs (signal-regulatory proteins) are a family of transmembrane glycoproteins that were identified by their association with the Src homology 2 domain-containing protein-tyrosine phosphatase SHP-2 in response to insulin. Here we examine whether SIRPalpha and SHP-2 are signaling molecules for the receptors for growth hormone (GH), leukemia inhibitory factor (LIF), or interferon-gamma (IFNgamma), cytokine receptor superfamily members that bind to and activate Janus kinase 2 (JAK2). In 3T3-F442A fibroblasts, GH rapidly stimulates tyrosyl phosphorylation of both SIRPalpha and SHP-2 and enhances association of SHP-2 with SIRPalpha. Consistent with JAK2 binding and phosphorylating SIRPalpha in response to GH, co-expression of SIRPalpha and JAK2 in COS cells results in tyrosyl phosphorylation of SIRPalpha and JAK2 association with SIRPalpha. LIF does not stimulate tyrosyl phosphorylation of SIRPalpha but stimulates greater tyrosyl phosphorylation of SHP-2 than GH. Additionally, LIF enhances association of SHP-2 with the gp130 subunit of the LIF receptor signaling complex. IFNgamma, which stimulates JAK2 to a greater extent than LIF, is ineffective at stimulating tyrosyl phosphorylation of SIRPalpha or SHP-2. These results suggest that SIRPalpha is a signaling molecule for GH but not for LIF or IFNgamma. Differential phosphorylation of SIRPalpha and SHP-2 may contribute to the distinct physiological effects of these ligands.Keywords
This publication has 34 references indexed in Scilit:
- Characterization of a 115-kDa Protein That Binds to SH-PTP2, a Protein-tyrosine Phosphatase with Src Homology 2 Domains, in Chinese Hamster Ovary CellsPublished by Elsevier BV ,1996
- Growth Hormone, Interferon-γ, and Leukemia Inhibitory Factor Utilize Insulin Receptor Substrate-2 in Intracellular SignalingPublished by Elsevier BV ,1996
- The SH2 Domain-containing Tyrosine Phosphatase PTP1D Is Required for Interferon α/β-induced Gene ExpressionPublished by Elsevier BV ,1996
- Adapter Function of Protein-tyrosine Phosphatase 1D in Insulin Receptor/Insulin Receptor Substrate-1 InteractionPublished by Elsevier BV ,1995
- Syp Associates with gp130 and Janus Kinase 2 in Response to Interleukin-11 in 3T3-L1 Mouse PreadipocytesPublished by Elsevier BV ,1995
- Identification of the Major SHPTP2-binding Protein That Is Tyrosine-phosphorylated in Response to InsulinPublished by Elsevier BV ,1995
- Identification of JAK2 as a growth hormone receptor-associated tyrosine kinaseCell, 1993
- SH2-Containing Phosphotyrosine Phosphatase as a Target of Protein-Tyrosine KinasesScience, 1993
- SH2 domains recognize specific phosphopeptide sequencesCell, 1993
- Growth hormone promoted tyrosyl phosphorylation of growth hormone receptors in murine 3T3-F442A fibroblasts and adipocytesBiochemistry, 1988