Evidence for autoinhibitory regulation of the c-src gene product. A possible interaction between the src homology 2 domain and autophosphorylation site.

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.

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Secondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR spectroscopy in solution.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.89.24.11673 ◽

1992 ◽

Vol 89 (24) ◽

pp. 11673-11677 ◽

Cited By ~ 20

Author(s):

M. Overduin ◽

B. Mayer ◽

C. B. Rios ◽

D. Baltimore ◽

D. Cowburn

Keyword(s):

Nmr Spectroscopy ◽

Secondary Structure ◽

Heteronuclear Nmr ◽

Src Homology 2 ◽

Heteronuclear Nmr Spectroscopy ◽

Src Homology ◽

Src Homology 2 Domain

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

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2021.01.129 ◽

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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Integrin-linked kinase (ILK) and src homology 2 domain-containing phosphatase 2 (SHP2): Novel targets in EGFR-mutation positive non-small cell lung cancer (NSCLC)

EBioMedicine ◽

10.1016/j.ebiom.2018.11.036 ◽

2019 ◽

Vol 39 ◽

pp. 207-214 ◽

Cited By ~ 13

Author(s):

Niki Karachaliou ◽

Andres Felipe Cardona ◽

Jillian Wilhelmina Paulina Bracht ◽

Erika Aldeguer ◽

Ana Drozdowskyj ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung ◽

Src Homology 2 ◽

Integrin Linked Kinase ◽

Src Homology ◽

Novel Targets ◽

Src Homology 2 Domain

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Structural Determinants of the Interaction between the erbB2 Receptor and the Src Homology 2 Domain of Grb7

Journal of Biological Chemistry ◽

10.1074/jbc.272.13.8490 ◽

1997 ◽

Vol 272 (13) ◽

pp. 8490-8497 ◽

Cited By ~ 54

Author(s):

Peter W. Janes ◽

Martin Lackmann ◽

W. Bret Church ◽

Georgina M. Sanderson ◽

Robert L. Sutherland ◽

...

Keyword(s):

Structural Determinants ◽

Src Homology 2 ◽

Erbb2 Receptor ◽

Src Homology ◽

Src Homology 2 Domain

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Differential Requirement for Adapter Proteins Src Homology 2 Domain-Containing Leukocyte Phosphoprotein of 76 kDa and Adhesion- and Degranulation-Promoting Adapter Protein in FcεRI Signaling and Mast Cell Function

The Journal of Immunology ◽

10.4049/jimmunol.172.11.6768 ◽

2004 ◽

Vol 172 (11) ◽

pp. 6768-6774 ◽

Cited By ~ 26

Author(s):

Jennifer N. Wu ◽

Martha S. Jordan ◽

Michael A. Silverman ◽

Erik J. Peterson ◽

Gary A. Koretzky

Keyword(s):

Mast Cell ◽

Cell Function ◽

Adapter Proteins ◽

Adapter Protein ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain

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Src homology 2 domain of overexpressed Lyn kinase is responsible for the acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation

Cell Biology International ◽

10.1016/j.cellbi.2006.02.009 ◽

2006 ◽

Vol 30 (6) ◽

pp. 525-532 ◽

Cited By ~ 1

Author(s):

N OKA ◽

A SUZUKI ◽

T OMURA ◽

H SAKAI ◽

H MURAKAMI

Keyword(s):

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Lyn Kinase ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Stimulating Factor

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Src homology 2 domain–containing inositol-5-phosphatase and CCAAT enhancer-binding protein β are targeted by miR-155 in B cells of Eμ-MiR-155 transgenic mice

Blood ◽

10.1182/blood-2009-05-220814 ◽

2009 ◽

Vol 114 (7) ◽

pp. 1374-1382 ◽

Cited By ~ 212

Author(s):

Stefan Costinean ◽

Sukhinder K. Sandhu ◽

Irene M. Pedersen ◽

Esmerina Tili ◽

Rossana Trotta ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

B Cells ◽

Transgenic Mice ◽

B Cell ◽

Lymphoblastic Leukemia ◽

High Grade ◽

Src Homology 2 ◽

Enhancer Binding Protein ◽

Src Homology ◽

Src Homology 2 Domain

AbstractWe showed that Eμ-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre–B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain–containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein β (C/EBPβ), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPβ, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

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