Homozygous mutant (Shp-2Delta46-110) embryonic stem (ES) cells exhibit decreased hematopoiesis; however, the point at which Shp-2 is critical for ES cell differentiation to hematopoietic cells is unknown. We characterized the differentiation defect of Shp-2Delta46-110 ES cells by examining early points of differentiation, conducting leukemia inhibitory factor (LIF)-stimulated biochemical analys...

The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) is an unusual orphan nuclear receptor that lacks a conventional DNA-binding domain and acts as a modulator of transcriptional activities of a number of nuclear receptors. We have previously reported that the orphan nuclear receptor ERRgamma activates the SHP promoter. In this study, we have found that basic helix-loop-helix (bHL...

Previously, we showed that Abl family tyrosine kinases are activated by growth factors, and Abl is required for transition from G1 to S phase during PDGF-mediated proliferation. Here, we show that the SHP-2 tyrosine phosphatase, which acts to promote proliferation in response to cytokines and growth factors, is a novel substrate of endogenous Abl kinases during growth factor-mediated cellular p...

Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are co...

The Src homology domain 2 (SH2)-containing tyrosine phosphatase SHP-2 has been implicated in the regulation of proliferation and differentiation in various cell types. Here, we investigated the ability of SHP-2 to mediate insulin-induced adipogenic differentiation of mouse 3T3-L1 cells. We found that the expression of SHP-2 was increased along with adipogenic differentiation. Overexpression of ...

Ciliary neurotrophic factor, along with other neuropoietic cytokines, signals through the shared receptor subunit gp130 [1-3], leading to the tyrosine phosphorylation of a number of substrates [4,5], including the transcription factors STAT1 and STAT3 and the protein tyrosine phosphatase SHP-2 [6,7] [8]. SHP-2 (also known as PTP1D, SHPTP2, Syp and PTP2C) is a positive regulatory molecule requir...

Amino acids are required for the activation of the mammalian target of rapamycin complex 1 (mTORC1), which plays a critical role in cell growth, proliferation, and metabolism. The branched-chain amino acid leucine is an essential nutrient that stimulates mTORC1 to promote protein synthesis by activating p70 S6 kinase 1 (S6K1). Here we show that the protein tyrosine phosphatase SHP-2 is required...

BACKGROUND Vascular endothelial growth factor receptor-2 (VEGFR-2, KDR), a receptor tyrosine kinase, regulates mitogenic, chemotactic, hyperpermeability, and survival signals in vascular endothelial cells in response to its ligand vascular permeability factor/ vascular endothelial growth factor (VPF/VEGF). SHP-1 is a protein tyrosine phosphatase known to negatively regulate signaling from recep...

Tyr phosphorylation of the multifunctional transmembrane protein band 3 has been implicated in several erythrocyte functions and disorders. We previously demonstrated that pervanadate treatment of human erythrocytes induces band-3 Tyr phosphorylation, which is catalyzed by the sequential action of tyrosine kinase Syk and tyrosine kinase(s) belonging to the Src family. In this study, we show tha...

Cholestasis activates bile acid receptor farnesoid X receptor (FXR) and subsequently enhances hepatic expression of small heterodimer partner (SHP). We previously demonstrated that SHP represses the transactivation of cytochrome P450 2D6 (CYP2D6) promoter by hepatocyte nuclear factor (HNF) 4α. In this study, we investigated the effects of estrogen-induced cholestasis on CYP2D6 expression. Estro...