The SRC homology regions (SH) 2 and 3, sequences conserved among noncatalytic regions of nonreceptor tyrosine kinases,
are found in a variety of oncogenic, signaling, and cellular substructure-associated proteins. Both the SH2 and SH3 domains
are considered to be involved in intermolecular interactions. ASH (abundant SRC homology), composed of one SH2 domain and two SH3 domains. The amino
acid sequence of ASH suggested that it is a mammalian homolog of Sem5, the product of a nematode gene responsible for
communication between a receptor protein tyrosine kinase and a Ras protein. ASH was thought to function as a similar
ubiquitous signal transducer. Induced expression of an antisense ASH cDNA led to a reduction in cell growth.
Gene whose expression is detected by cDNA array hybridization: transporters, signal transduction. Also, relative transcript level reproducibly decreases during IVM Rozenn Dalbis-Tran and Pascal Mermilloda
Expression regulated by
LH
Comment
Carvalho CR, et al reported a novel signal transduction pathway for luteinizing hormone and its interaction with insulin and the activation of Janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/Akt pathways.
The actions of LH are mediated through a single class of cell surface LH/human chorionic gonadotropin receptor, which is a member of the G protein-coupled receptor family. In the present study the authors showed that LH induced rapid tyrosine phosphorylation and activation of the Janus kinase 2 (JAK2) in rat ovary. Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. In addition, LH induced IRS-1/phosphoinositol 3-kinase and Shc /growth factor receptor-binding protein 2 (Grb2) associations and downstream AKT (protein kinase B, homologous to v-AKT) serine phosphorylation and ERK tyrosine phosphorylation, respectively. The simultaneous infusion of insulin and LH induced higher phosphorylation levels of JAK2, STAT5b, IRS-1, and AKT compared with each hormone alone in the whole ovary of normal rats. By immunohistochemistry the authors demonstrated that these late events take place in follicular cells and both external and internal theca. These results indicate a new signal transduction pathway for LH and show that there is positive cross-talk between the insulin and LH signaling pathways at the level of phosphoinositol 3-kinase/AKT pathway in this tissue.
Ovarian localization
Theca
Comment
GRB2 is abundent in an ovary cDNA library.
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment: By targeted disruption, Cheng et al. (1998) introduced a null mutation into the mouse gene for Grb2. Analysis of mutant
embryonic stem cells, embryos, and chimeras revealed that Grb2 is required during embryogenesis for the
differentiation of endodermal cells and formation of the epiblast.