scholarly journals Enzymatic Activity of the Src Homology 2 Domain-containing Inositol Phosphatase Is Regulated by a Plasma Membrane Location

2000 ◽  
Vol 275 (25) ◽  
pp. 19090-19097 ◽  
Author(s):  
Hyewon Phee ◽  
Anand Jacob ◽  
K. Mark Coggeshall
Keyword(s):  
Plasma Membrane ◽  
Enzymatic Activity ◽  
Inositol Phosphatase ◽  
Src Homology 2 ◽  
Src Homology ◽  
Membrane Location ◽  
Src Homology 2 Domain

scholarly journals Differential Regulation of B Cell Development, Activation, and Death by the Src Homology 2 Domain–Containing 5′ Inositol Phosphatase (Ship)

2000 ◽  
Vol 191 (9) ◽  
pp. 1545-1554 ◽  
Author(s):  
Anne Brauweiler ◽  
Idan Tamir ◽  
Joseph Dal Porto ◽  
Robert J. Benschop ◽  
Cheryl D. Helgason ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Inositol Phosphatase ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain ◽  
Deficient Mice

Although the Src homology 2 domain–containing 5′ inositol phosphatase (SHIP) is a well-known mediator of inhibitory signals after B cell antigen receptor (BCR) coaggregation with the low affinity Fc receptor, it is not known whether SHIP functions to inhibit signals after stimulation through the BCR alone. Here, we show using gene-ablated mice that SHIP is a crucial regulator of BCR-mediated signaling, B cell activation, and B cell development. We demonstrate a critical role for SHIP in termination of phosphatidylinositol 3,4,5-triphosphate (PI[3,4,5]P3) signals that follow BCR aggregation. Consistent with enhanced PI(3,4,5)P3 signaling, we find that splenic B cells from SHIP-deficient mice display enhanced sensitivity to BCR-mediated induction of the activation markers CD86 and CD69. We further demonstrate that SHIP regulates the rate of B cell development in the bone marrow and spleen, as B cell precursors from SHIP-deficient mice progress more rapidly through the immature and transitional developmental stages. Finally, we observe that SHIP-deficient B cells have increased resistance to BCR-mediated cell death. These results demonstrate a central role for SHIP in regulation of BCR signaling and B cell biology, from signal driven development in the bone marrow and spleen, to activation and death in the periphery.

scholarly journals The Src Homology 2 Domain of Vav Is Required for Its Compartmentation to the Plasma Membrane and Activation of C-Jun Nh2-Terminal Kinase 1

2000 ◽  
Vol 191 (1) ◽  
pp. 47-60 ◽  
Author(s):  
Ramachandran Arudchandran ◽  
Martin J. Brown ◽  
Matthew J. Peirce ◽  
James S. Song ◽  
Juan Zhang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adaptor Protein ◽  
Sh2 Domain ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Src Homology 2 ◽  
Nucleotide Exchange Factor ◽  
Downstream Effectors ◽  
Src Homology ◽  
Src Homology 2 Domain

Vav is a hematopoietic cell–specific guanine nucleotide exchange factor (GEF) whose activation is mediated by receptor engagement. The relationship of Vav localization to its function is presently unclear. We found that Vav redistributes to the plasma membrane in response to Fc∈ receptor I (Fc∈RI) engagement. The redistribution of Vav was mediated by its Src homology 2 (SH2) domain and required Syk activity. The Fc∈RI and Vav were found to colocalize and were recruited to glycosphingolipid-enriched microdomains (GEMs). The scaffold protein, linker for activation of T cells (LAT), and Rac1 (a target of Vav activity) were constitutively present in GEMs. Expression of an SH2 domain–containing COOH-terminal fragment of Vav inhibited Vav phosphorylation and movement to the GEMs but had no effect on the tyrosine phosphorylation of the adaptor protein, SLP-76 (SH2 domain–containing leukocyte protein of 76 kD), and LAT. However, assembly of the multiprotein complex containing these proteins was inhibited. In addition, Fc∈RI-dependent activation of c-Jun NH2-terminal kinase 1 (JNK1) was also inhibited. Thus, Vav localization to the plasma membrane is mediated by its SH2 domain and may serve to regulate downstream effectors like JNK1.

scholarly journals IL-6 blocks a discrete early step in lymphopoiesis

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 879-885 ◽  
Author(s):  
Kazuhiko Maeda ◽  
Yoshihiro Baba ◽  
Yoshinori Nagai ◽  
Kozo Miyazaki ◽  
Alexander Malykhin ◽  
...  
Keyword(s):  
Target Cells ◽  
Hematopoietic Progenitors ◽  
Early Step ◽  
Hematopoietic Stem ◽  
Lymphoid Lineage ◽  
Src Homology 2 ◽  
Multipotent Progenitors ◽  
Src Homology ◽  
Src Homology 2 Domain

Abstract Animals lacking Src homology 2 domain-containing inositol 5-phosphatase (SHIP) display a reduction in lymphopoiesis and a corresponding enhancement of myelopoiesis. These effects are mediated at least in part by elevated levels of interleukin 6 (IL-6). Here, we show the lymphopoiesis block in SHIP–/– mice is due to suppression of the lymphoid lineage choice by uncommitted progenitors. The suppression can be reproduced in vitro with recombinant IL-6, and IL-6 acts directly on hematopoietic progenitors. The block is partially overcome in SHIP–/– IL-6–/– double-deficient animals. IL-6 does not suppress but actually enhances proliferation of lymphoid-committed progenitors, indicating the IL-6 target cells are hematopoietic stem cells or multipotent progenitors. The findings suggest a mechanism for the lymphopenia that accompanies proinflammatory diseases.

scholarly journals FP12.03 SRC-Homology 2 Domain-Containing Phosphatase 2 (SHP2) in Resected Lung Adenocarcinoma (LUAD)

2021 ◽  
Vol 16 (3) ◽  
pp. S217-S218
Author(s):  
M. Ito ◽  
J. Codony-Servat ◽  
A. Giménez-Capitán ◽  
M. Serra-Mitjans ◽  
F. Pérez-Ochoa ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain
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