Involvement of SHP-2 in multiple aspects of IL-2 signaling: evidence for a positive regulatory role

M Gadina; L M Stancato; C M Bacon; A C Larner; J J O'Shea

Involvement of SHP-2 in multiple aspects of IL-2 signaling: evidence for a positive regulatory role

J Immunol. 1998 May 15;160(10):4657-61.

Authors

M Gadina¹, L M Stancato, C M Bacon, A C Larner, J J O'Shea

Affiliation

¹ Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. [email protected]

PMID: 9590209

Abstract

Binding of IL-2 to its receptor activates several biochemical pathways, but precisely how these pathways are linked is incompletely understood. Here, we report that SHP-2, an SH2-domain containing tyrosine phosphatase, associates with different molecules of the IL-2 signaling cascade. Upon IL-2 stimulation, SHP-2 was coimmunoprecipitated with Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. In contrast, SHP-2 was constitutively associated with JAK1 and JAK3. Finally, SHP-2 expression amplified STAT-dependent transcriptional activation whereas a dominant negative allele inhibited transactivation and the IL-2-induced activation of MAPK (mitogen-activated protein kinase). These results demonstrate the involvement of SHP-2 in multiple pathways of the IL-2 signaling cascade and provide evidence for its positive regulatory role.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing*
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
Cells, Cultured
Enzyme Activation
GRB2 Adaptor Protein
Humans
Interleukin-2 / pharmacology*
Intracellular Signaling Peptides and Proteins
Janus Kinase 3
Phosphatidylinositol 3-Kinases / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / physiology*
Protein-Tyrosine Kinases / metabolism
Proteins / metabolism
SH2 Domain-Containing Protein Tyrosine Phosphatases
Transcriptional Activation

Substances

Adaptor Proteins, Signal Transducing
GRB2 Adaptor Protein
GRB2 protein, human
Interleukin-2
Intracellular Signaling Peptides and Proteins
Proteins
Phosphatidylinositol 3-Kinases
Protein-Tyrosine Kinases
JAK3 protein, human
Janus Kinase 3
Calcium-Calmodulin-Dependent Protein Kinases
PTPN11 protein, human
PTPN6 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases
SH2 Domain-Containing Protein Tyrosine Phosphatases