Negative Regulation of Growth Hormone Receptor/JAK2 Signaling by Signal Regulatory Protein α

Abstract

SUMMARYSIRPs (signal regulatory proteins) are receptor-like transmembrane proteins, the majority of which contain a cytoplasmic proline-rich region and four cytoplasmic tyrosines that, when phosphorylated, bind SH2 domain-containing protein tyrosine phosphatases (SHP). We Consistent with reduced JAK2 activity, overexpression of wild-type SIRPα1 but not SIRP 4YF reduces GH-induced phosphorylation of ERKs 1 and 2, STAT3 and STAT5B. These results suggest that SIRPα1 is a negative regulator of GH signaling and that the ability of SIRPα1

Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation

“…SIRPα is one of over a dozen SIRP members belonging to the transmembrane immunoglobulin superfamily, and it possesses a C-terminal intracellular domain containing four tyrosine residues that form two immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Similar to other ITIM domain containing proteins, SIRPα has been implicated in both positive and negative regulation of cellular responses to a wide variety of different stimuli through ligand induced interactions with tyrosine phosphatase-1 or 2 (SHP-1 and 2) (Stofega et al 2000). We have observed that no SIRPα-CD47 binding interactions can result in inhibited or enhanced PMN transmigration due to bi-directional signaling pathways with different functional consequences depending on how the ligand is presented.…”

Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

“…Studies in transfected cells over expressing either wild type Shp2, or Shp2 forms defective for one of its molecular functions, suggested that the phosphatase could act as a negative regulator of GH receptor signaling, possibly by dephosphorylating STAT5A [62,63]. Nevertheless, although these findings have been reported more than ten years ago, they remain to be validated in different cell types and in animal models.…”

Transcriptomics of salinity tolerance capacity in Arctic charr (Salvelinus alpinus): a comparison of gene expression profiles between divergent QTL genotypes

“…MAPK14, which was slightly upregulated (i.e., 1.7ϫ) in high salinity tolerance capacity fish and colocalized with a QTL on AC-1/11, forms a complex with NKCC1 in the nerve cells that dissociates upon cellular stress (50). PTPN11, also upregulated in high salinity tolerance capacity fish (i.e., 45ϫ), negatively regulates GHR signaling (61). Considering that genes in eukaryotic genomes are arranged in clusters that tend to be coexpressed (45,68) and comethylated (44) and in light of interactions that occur between candidate genes and differentially expressed genes, it is likely that the candidate genes and differentially expressed genes are involved in the same or closely related biological pathways.…”