Bruton tyrosine kinase (BTK; 300300) is a cytoplasmic tyrosine kinase crucial for the maturation of B-lineage cells. BTK deficiency is involved in the pathogenesis of X-linked immunodeficiency. By Far Western expression cloning using a human placenta cDNA library for molecules associated with the SH3 domain of BTK, followed by screening brain and B-cell cDNA libraries, Matsushita et al. (1998) obtained a cDNA encoding SH3BP5, which they termed SAB (SH3 domain-binding protein that preferentially associates with BTK). SH3BP5 encodes a deduced 425-amino acid protein. Northern blot analysis revealed wide expression of a 3.0-kb transcript, with especially prominent expression in testis and ovary. Immunoblot analysis showed that SH3BP5 is expressed as a 70-kD protein. Immunoprecipitation analysis suggested that SH3BP5 interacts with BTK in cells. Mutational and immunoblot analyses showed that amino acids 163 to 193 of SH3BP5 bind most strongly to the SH3 domain of BTK and not with the SH3 domains of a number of other cytoplasmic tyrosine kinases.
General function
Intracellular signaling cascade
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Cellular localization
Cytoplasmic
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Ovarian function
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Expression regulated by
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Polycystic ovary syndrome (PCOS) affects 5% of reproductive aged women and is the leading cause of anovulatory infertility. A hallmark of PCOS is excessive theca cell androgen secretion, which is directly linked to the symptoms of PCOS. Our previous studies demonstrated that theca cells from PCOS ovaries maintained in long term culture persistently secrete significantly greater amounts of androgens than normal theca cells, suggesting an intrinsic abnormality. Furthermore, previous studies suggested that ovarian hyperandrogenemia is inherited as an autosomal dominant trait. However, the genes responsible for ovarian hyperandrogenemia of PCOS have not been identified. In this present study, Wood JR, et al carried out microarray analysis to define the gene networks involved in excess androgen synthesis by the PCOS theca cells in order to identify candidate PCOS genes. Analysis revealed that PCOS theca cells have a gene expression profile that is distinct from normal theca cells. Included in the cohort of genes with increased mRNA abundance in PCOS theca cells were aldehyde dehydrogenase 6 and retinol dehydrogenase 2, which play a role in all-trans-retinoic acid biosynthesis and the transcription factor GATA6. We demonstrated that retinoic acid and GATA6 increased the expression of 17alpha-hydroxylase, providing a functional link between altered gene expression and intrinsic abnormalities in PCOS theca cells. Thus, the analyses have 1) defined a stable molecular phenotype of PCOS theca cells, 2) suggested new mechanisms for excess androgen synthesis by PCOS theca cells, and 3) identified new candidate genes that may be involved in the genetic etiology of PCOS. This is one of the genes with Altered mRNA Abundance in PCOS Theca Cells as compared with normal theca cells Maintained Under Basal Conditions.
Ovarian localization
Theca
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Follicle stages
Primordial
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Arraztoa JA, et al 2005 reported the identification of genes expressed in primate primordial oocytes.