scholarly journals Phosphorylation of Ser24in the Pleckstrin Homology Domain of Insulin Receptor Substrate-1 by Mouse Pelle-like Kinase/Interleukin-1 Receptor-associated Kinase

2005 ◽  
Vol 280 (24) ◽  
pp. 23173-23183 ◽  
Author(s):  
Jeong-a Kim ◽  
Deborah C. Yeh ◽  
Marel Ver ◽  
Yunhua Li ◽  
Andrea Carranza ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Interleukin 1 ◽  
Pleckstrin Homology Domain ◽  
Insulin Receptor Substrate ◽  
Pleckstrin Homology ◽  
Insulin Receptor Substrate 1

scholarly journals Identification of SH2B2β as an Inhibitor for SH2B1- and SH2B2α-Promoted Janus Kinase-2 Activation and Insulin Signaling

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1615-1621 ◽  
Author(s):  
Minghua Li ◽  
Zhiqin Li ◽  
David L. Morris ◽  
Liangyou Rui
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Insulin Signaling ◽  
Sh2 Domain ◽  
Janus Kinase ◽  
Pleckstrin Homology Domain ◽  
Insulin Receptor Substrate ◽  
Janus Kinase 2 ◽  
Pleckstrin Homology ◽  
Insulin Receptor Substrate 1

The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain mediates the formation of homo- and heterodimers between members of the SH2B family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases, including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the activation of JAK2 or the insulin receptor, respectively. JAK2 binds to various members of the cytokine receptor family, including receptors for GH and leptin, to mediate cytokine responses. In mice, SH2B1 regulates energy and glucose homeostasis by enhancing leptin and insulin sensitivity. In this work, we identify SH2B2β as a new isoform of SH2B2 (designated as SH2B2α) derived from the SH2B2 gene by alternative mRNA splicing. SH2B2β has a DD and pleckstrin homology domain but lacks a SH2 domain. SH2B2β bound to both SH2B1 and SH2B2α, as demonstrated by both the interaction of glutathione S-transferase-SH2B2β fusion protein with SH2B1 or SH2B2α in vitro and coimmunoprecipitation of SH2B2β with SH2B1 or SH2B2α in intact cells. SH2B2β markedly attenuated the ability of SH2B1 to promote JAK2 activation and subsequent tyrosine phosphorylation of insulin receptor substrate-1 by JAK2. SH2B2β also significantly inhibited SH2B1- or SH2B2α-promoted insulin signaling, including insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1. These data suggest that SH2B2β is an endogenous inhibitor of SH2B1 and/or SH2B2α, negatively regulating insulin signaling and/or JAK2-mediated cellular responses.

scholarly journals Regulation of Insulin Receptor Substrate 1 Pleckstrin Homology Domain by Protein Kinase C: Role of Serine 24 Phosphorylation

2006 ◽  
Vol 20 (8) ◽  
pp. 1838-1852 ◽  
Author(s):  
Ranmali Nawaratne ◽  
Alexander Gray ◽  
Christina H. Jørgensen ◽  
C. Peter Downes ◽  
Kenneth Siddle ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Pleckstrin Homology Domain ◽  
Insulin Receptor Substrate ◽  
Pleckstrin Homology ◽  
Insulin Receptor Substrate 1 ◽  
Kinase C

scholarly journals The Pleckstrin Homology Domain in Insulin Receptor Substrate-1 Sensitizes Insulin Signaling

1995 ◽  
Vol 270 (20) ◽  
pp. 11715-11718 ◽  
Author(s):  
Martin G. Myers ◽  
Timothy C. Grammer ◽  
Jennifer Brooks ◽  
Erin M. Glasheen ◽  
Ling-Mei Wang ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Insulin Signaling ◽  
Pleckstrin Homology Domain ◽  
Insulin Receptor Substrate ◽  
Pleckstrin Homology ◽  
Insulin Receptor Substrate 1

scholarly journals Role of Pleckstrin Homology Domain in Regulating Membrane Targeting and Metabolic Function of Insulin Receptor Substrate 3

2003 ◽  
Vol 17 (8) ◽  
pp. 1568-1579 ◽  
Author(s):  
Tania Maffucci ◽  
Giorgia Razzini ◽  
Alessandra Ingrosso ◽  
Hui Chen ◽  
Stefano Iacobelli ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Pleckstrin Homology Domain ◽  
Membrane Targeting ◽  
Insulin Receptor Substrate ◽  
Metabolic Function ◽  
Pleckstrin Homology

scholarly journals Cloning and Characterization of PHIP, a Novel Insulin Receptor Substrate-1 Pleckstrin Homology DomainInteracting Protein

2000 ◽  
Vol 275 (51) ◽  
pp. 40492-40497 ◽  
Author(s):  
Janet Farhang-Fallah ◽  
Xianhua Yin ◽  
Grace Trentin ◽  
Alec M. Cheng ◽  
Maria Rozakis-Adcock
Keyword(s):  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Pleckstrin Homology ◽  
Insulin Receptor Substrate 1
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