Aquilegia, Vol. 20 No. 2, April-June 1996: Newsletter of the Colorado Native Plant Society

https://epublications.regis.edu/aquilegia/1079/thumbnail.jp

Aquilegia, Vol. 19 No. 1, January-March 1995: Newsletter of the Colorado Native Plant Society

https://epublications.regis.edu/aquilegia/1074/thumbnail.jp

Aquilegia, Vol. 18 No. 5, September-December 1994: Newsletter of the Colorado Native Plant Society

https://epublications.regis.edu/aquilegia/1073/thumbnail.jp

Aquilegia, Vol. 19 No. 2, April-June 1995: Newsletter of the Colorado Native Plant Society

https://epublications.regis.edu/aquilegia/1075/thumbnail.jp

Congenic interval of CD45/Ly-5 congenic mice contains multiple genes that may influence hematopoietic stem cell engraftment

The B6.SJL-Ptprc(d)Pep3(b)/BoyJ (B6.SJL) congenic mouse strain, a valuable and widely used tool in murine bone marrow transplantation studies, has long been considered equivalent to the parental C57B/L6 (B6) strain with the exception of a small congenic interval on chromosome 1 harboring an alternative CD45/Ly-5 alloantigen (Ly-5.1). In this study we compared functional properties of stem and stromal cells between the strains, and delineated the boundary of the B6.SJL congenic interval. We identified a 25% reduction in homing efficiency, 3.8-fold reduction in transplantable long-term hematopoietic stem cells (LT-HSCs), a 5-fold reduction in LT-HSCs capable of 24-hour homing, and a cell-intrinsic engraftment defect of 30% to 50% in B6.SJL-derived bone marrow cells relative to B6-derived cells. These functional differences were independent of stem cell number, cycling, or apoptosis. Genotypic analysis revealed a 42.1-mbp congenic interval in B6.SJL including 306 genes, and at least 124 genetic polymorphisms. Moreover, expression profiling revealed 288 genes differentially expressed between nonhematopoietic stromal cells of the 2 strains. These results indicate that polymorphisms between the B6 and SJL genotype within the B6.SJL congenic interval influence HSC engraftment and result in transcriptional variation within bone marrow stroma

Mechanism of activation of PKB/Akt by the protein phosphatase inhibitor Calyculin A

The protein phosphatase inhibitor calyculin A activates PKB/Akt to ~50% of the activity induced by insulin-like growth factor 1 (IGF1) in HeLa cells promoting an evident increased phosphorylation of Ser473 despite the apparent lack of Thr308 phosphorylation of PKB. Nevertheless, calyculin A-induced activation of PKB seems to be dependent on basal levels of Thr308 phosphorylation, since a PDK1-dependent mechanism is required for calyculin A-dependent PKB activation by using embryonic stem cells derived from PDK1 wild-type and knockout mice. Data shown suggest that calyculin A-induced phosphorylation of Ser473 was largely blocked by LY294002 and SB-203580 inhibitors, indicating that both PI3-kinase/TORC2-dependent and SAPK2/p38-dependent protein kinases contributed to phosphorylation of Ser473 in calyculin A-treated cells. Additionally, our results suggest that calyculin A blocks the IGF1-dependent Thr308 phosphorylation and activation of PKB, likely due to an enhanced Ser612 phosphorylation of insulin receptor substrate 1 (IRS1), which can be inhibitory to its activation of PI3-kinase, a requirement for PDK1-induced Thr308 phosphorylation and IGF1-dependent activation of PKB. Our data suggest that PKB activity is most dependent on the level of Ser473 phosphorylation rather than Thr308, but basal levels of Thr308 phosphorylation are a requirement. Additionally, we suggest here that calyculin A regulates the IGF1-dependent PKB activation by controlling the PI3-kinase-associated IRS1 Ser/Thr phosphorylation levels. © 2010 Springer Science+Business Media, LLC.We thank the European Community programme ‘‘Quality of Life and Management of Living Resources’’ for a Marie Curie Fellowship (QLK1-CT-2000-51184), ‘‘Ministerio de Educación y Ciencia’’ grant BFU2006-01088/BMC and ‘‘Programa Ramón y Cajal’’ contract (B.O.E. 17/02/2004 ORDEN CTE/351/2004) to Mercedes Pozuelo Rubio.Peer Reviewe