The LIM/Homeodomain Protein Islet1 Recruits Janus Tyrosine Kinases and Signal Transducer and Activator of Transcription 3 and Stimulates Their Activities

Abstract

Islet1 (Isl1) belongs to the LIM homeodomain transcription factor family. Its roles in differentiation of motor neurons and organogenesis of pancreas and heart have been revealed. However, less is known about its regulatory mechanism and the target genes. In this study, we identified interactions between Isl1 and Janus tyrosine kinase (JAK), as well as signal transducer and activator of transcription (Stat)3, but not Stat1 and Stat5, in mammalian cells. We found that Isl1 not only forms a complex with Jak1 and Stat3 but also triggers the tyrosine phosphorylation of Jak1 and its kinase activity, thereby elevating the tyrosine phosphorylation, DNA binding activity, and target gene expression of Stat3. In vivo, the tyrosine-

The LIM-Homeodomain Protein ISL1 Activates Insulin Gene Promoter Directly through Synergy with BETA2

“…In a complex of JAK1, ISL1, and STAT3, the LIM1 and LIM2 domains of ISL1 together strongly mediated the interaction with STAT3 and the homeodomain of ISL1 also interacted with STAT3. 23 However, the homeodomain of ISL1 is dispensable for the interaction with estrogen receptor (ER), consistent with our results. We also showed that LIM1 and LIM2 deletion enhanced the transcriptional activation of the ISL1 protein alone or synergistically with BETA2 by luciferase assays.…”

“…The surprising synergy between ISL1 without LIM interaction domains and BETA2 also suggests that there could be some other unidentified proteins in the complex of ISL1 and BETA2, which probably mediate the synergic activity between ISL1 and BETA2, as it has been reported that the homeodomain of ISL1 could also interact with other proteins. 23 However, the detailed mechanism remained to be investigated.…”

LIM-homeodomain Transcription Factor Isl-1 Mediates the Effect of Leptin on Insulin Secretion in Mice

“…It has been reported that STAT3 functions as a transcriptional activator or as a transcriptional inhibitor by its interacting with other transcription factors and/or co-activators/corepressors, depending on the target promoter (47), whereas Isl-1 not only forms a complex with JAK1 and STAT3 but also triggers tyrosine phosphorylation of JAK and its kinase activity to elevate tyrosine phosphorylation and DNA binding activity and target gene expression of STAT3 (41). However, it had not been established about the interacting mechanism between leptin signaling molecule STAT3 and Isl-1.…”

Oct4 is expressed in human gliomas and promotes colony formation in glioma cells

“…C6 glioma cells were cultured in DMEM/F12 (Hyclone Co.) containing 10% fetal bovine serum. Rat neural stem cells (NSCs) and astrocytes were cultured as described previously (McCarthy and de Vellis, 1980;Palmer et al, 1997 Biomedicine, Germany), and the Stat3 expression plasmid pXJ40-HA-Stat3 was constructed as described by us previously (Hao et al, 2005). Transfection of siRNA or plasmid was carried out using Lipofectamine 2000 (Invitrogen) according to the manufacturer's instructions.…”