Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary SLI was measured every six hours for twenty four hours in rats fed a regular diet. Previously, we found that the urinary SLI increased after the administration of TRH intravenously. In the present study, in order to reveal the localization of increased SLI, we measured the contents in the hypothalamus, pituitary, thyroid, stomach and pancreas after the oral TRH administration. (1) The rat urinary SLI levels showed a circadian rhythm. The maximum level of SLI was collected from 0.00--6.00 a.m. (89.4 +/- 8.6 pg/6 hrs) (mean +/- SEM). This level was reduced during the daytime 6.00 a.m.--6.00 p.m. The minimum level was obtained from 6.00 p.m.--0.00 a.m. (49.3 +/- 7.2 pg/6 hrs). (2) The rats were decapitated at three and six hours after the oral TRH (500 micrograms/ml) administration. The SLI content was measured by RIA after extraction from each organ with 2.5 ml of 2 M acetic acid. The pituitary SLI content was reduced three hours after the oral TRH administration. The thyroid SLI content was reduced six hours after the oral TRH administration. The hypothalamic, gastric and pancreatic SLI contents didn't change at three and six hours after the oral TRH administration. As the result, the data suggest that augmentation by the oral TRH administration of urinary SLI was caused by its effect on the both the pituitary and the thyroid.
 ...
PMID:[Circadian rhythm of urinary somatostatin-like immunoreactivity (SLI) and its contents in several organs after oral TRH administration in rats]. 641 98

Vulval induction in Caenorhabditis elegans has helped define an evolutionarily conserved signal transduction pathway from receptor tyrosine kinases (RTKs) through the adaptor protein SEM-5 to RAS. One component present in other organisms, a guanine nucleotide exchange factor for Ras, has been missing in C.ELEGANS: To understand the regulation of this pathway it is crucial to have all positive-acting components in hand. Here we describe the identification, cloning and genetic characterization of C.ELEGANS: SOS-1, a putative guanine nucleotide exchanger for LET-60 RAS. RNA interference experiments suggest that SOS-1 participates in RAS-dependent signaling events downstream of LET-23 EGFR, EGL-15 FGFR and an unknown RTK. We demonstrate that the previously identified let-341 gene encodes SOS-1. Analyzing vulval development in a let-341 null mutant, we find an SOS-1-independent pathway involved in the activation of RAS signaling. This SOS-1-independent signaling is not inhibited by SLI-1/Cbl and is not mediated by PTP-2/SHP, raising the possibility that there could be another RasGEF.
 ...
PMID:Caenorhabditis elegans SOS-1 is necessary for multiple RAS-mediated developmental signals. 1088 Apr 41

SLI-1, a Caenorhabditis elegans homologue of the proto-oncogene product c-Cbl, is a negative regulator of LET-23-mediated vulval differentiation. Lack of SLI-1 activity can compensate for decreased function of the LET-23 epidermal growth factor receptor, the SEM-5 adaptor, but not the LET-60 RAS, suggesting that SLI-1 acts before RAS activation. SLI-1 and c-Cbl comprise an N-terminal region (termed SLI-1:N/Cbl-N, containing a four-helix bundle, an EF hand calcium-binding domain, and a divergent SH2 domain) followed by a RING finger domain and a proline-rich C-terminus. In a transgenic functional assay, the proline-rich C-terminal domain is not essential for sli-1(+) function. A protein lacking the SH2 and RING finger domains has no activity, but a chimeric protein with the SH2 and RING finger domains of SLI-1 replaced by the equivalent domains of c-Cbl has activity. The RING finger domain of c-Cbl has been shown recently to enhance ubiquitination of active RTKs by acting as an E3 ubiquitin-protein ligase. We find that the RING finger domain of SLI-1 is partially dispensable. Further, we identify an inhibitory tyrosine of LET-23 requiring sli-1(+) for its effects: removal of this tyrosine closely mimics the loss of sli-1 but not of another negative regulator, ark-1. Thus, we suggest that this inhibitory tyrosine mediates its effects through SLI-1, which in turn inhibits signaling upstream of LET-60 RAS in a manner not wholly dependent on the ubiquitin-ligase domain.
 ...
PMID:Requirements of multiple domains of SLI-1, a Caenorhabditis elegans homologue of c-Cbl, and an inhibitory tyrosine in LET-23 in regulating vulval differentiation. 1107 24