title: Reduced Tyk2/SHP-1 interaction and lack of SHP-1 mutation in a kindred of familial hemophagocytic lymphohistiocytosis.
abstract: Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive disease with features similar to those of the murine motheaten phenotype resulting from mutations of protein tyrosine phosphatase SHP-1. This has raised the possibility that defects in SHP-1 or SHP-1-regulated signaling molecules may be present in FHLH. In this study, we examined SHP-1 protein and transcript in the peripheral blood mononuclear cells (PBMC) of an FHLH family. Our results show that the FHLH patient and the parents express comparable levels of a single SHP-1 protein and that the SHP-1 cDNA clone from the patient contains no mutation in the coding region. Interestingly, a reduced association of SHP-1 with the Jak family kinase Tyk2 was detected in the patient and the defect appears to have been inherited from one of the parents. This reduced SHP-1/Tyk2 association is likely due to a defect in Tyk2 or in cellular factors regulating Tyk2, because we found no abnormalities in SHP-1 or in SHP-1 association with the other Jak kinases. These data demonstrate that the SHP-1 gene is intact in FHLH and that the defect in some cases with this disease may involve signaling molecules regulated by SHP-1.
authors.affiliation: Department of Cancer Biology, The Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tabrizi
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Jiao
authors.forename: E M
authors.initials: EM
authors.lastname: DeVries
authors.forename: L C
authors.initials: LC
authors.lastname: Platanias
authors.forename: M
authors.initials: M
authors.lastname: Arico
authors.forename: T
authors.initials: T
authors.lastname: Yi
mesh_terms: D000328:Adult; D000818:Animals; D019556:COS Cells / Q000378:metabolism; D002648:Child; D018076:DNA, Complementary / Q000235:genetics; D015616:Histiocytosis, Non-Langerhans-Cell / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D009154:Mutation; D010375:Pedigree; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D053634:TYK2 Kinase
chemical_list: D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases