title: STK25 is a candidate gene for pseudopseudohypoparathyroidism.
abstract: We determined the chromosomal location of the mouse gene Stk25, encoding a member of the Ste20/PAK family of serine/threonine kinases, by interspecific backcross analysis. We mapped Stk25 to the central region of mouse chromosome 1 linked to Chrng (formerly Acrg) and En1. This central region of mouse chromosome 1 shares a region of homology with the long arm of human chromosome 2, suggesting that the human homologue of Stk25 would also map to 2q. We proved this prediction of syntenic homology correct by mapping human STK25 to 2q37. Deletion of the 2q37 region has been implicated in the expression of pseudopseudohypoparathyroidism (PPHP), a disease which shares features of the Albright hereditary osteodystrophy (AHO) phenotype. To investigate a pathogenetic relationship between STK25 and PPHP, we carried out fluorescence in situ hybridization (FISH) using an STK25 gene probe and chromosomes from PPHP patients characterized as having small deletions near the distal end of 2q. PPHP patient DNA showed no hybridization to STK25 genomic DNA, indicating that STK25 is contained within the deleted chromosomal region. This finding, in conjunction with previous studies demonstrating the role of Ste20/PAK kinases in heterotrimeric G protein signaling, suggests that STK25 is a positional candidate gene for PPHP.
authors.affiliation: Cell Signaling Technology, Beverly, Massachusetts 01915, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Davids
authors.forename: E
authors.initials: E
authors.lastname: Crawford
authors.forename: S
authors.initials: S
authors.lastname: Weremowicz
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: D J
authors.initials: DJ
authors.lastname: Gilbert
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: M C
authors.initials: MC
authors.lastname: Phelan
authors.forename: M J
authors.initials: MJ
authors.lastname: Comb
authors.forename: M B
authors.initials: MB
authors.lastname: Melnick
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009115:Muridae; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011556:Pseudopseudohypoparathyroidism / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae