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

This review will describe the SH2-domain signaling protein Src Homology-2 domain containing protein B (SHB) and its role in various physiological processes relating in particular to glucose homeostasis and β cell function. SHB operates downstream of several tyrosine kinase receptors and assembles signaling complexes in response to receptor activation by interacting with other signaling proteins via its other domains (proline-rich, phosphotyrosine-binding and tyrosine-phosphorylation sites). The subsequent responses are context-dependent. Absence ofShbin mice has been found to exert effects on hematopoiesis, angiogenesis and glucose metabolism. Specifically, first-phase insulin secretion in response to glucose was impaired and this effect was related to altered characteristics of focal adhesion kinase activation modulating signaling through Akt, ERK, β catenin and cAMP. It is believed that SHB plays a role in integrating adaptive responses to various stimuli by simultaneously modulating cellular responses in different cell-types, thus playing a role in maintaining physiological homeostasis.

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The Src Homology 2 Domain-Containing Adapter Protein B (SHB) Regulates Mouse Oocyte Maturation

PLoS ONE ◽

10.1371/journal.pone.0011155 ◽

2010 ◽

Vol 5 (6) ◽

pp. e11155 ◽

Cited By ~ 13

Author(s):

Gabriela Calounova ◽

Gabriel Livera ◽

Xiao-Qun Zhang ◽

Kui Liu ◽

Roger G. Gosden ◽

...

Keyword(s):

Oocyte Maturation ◽

Mouse Oocyte ◽

Adapter Protein ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Protein B

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Direct analysis of the binding of the abl Src homology 2 domain to the activated epidermal growth factor receptor.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)53920-x ◽

1993 ◽

Vol 268 (3) ◽

pp. 1775-1779 ◽

Cited By ~ 1

Author(s):

G. Zhu ◽

S.J. Decker ◽

B.J. Mayer ◽

A.R. Saltiel

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Direct Analysis ◽

Src Homology 2 ◽

Src Homology ◽

Epidermal Growth ◽

Src Homology 2 Domain

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

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)54051-5 ◽

1993 ◽

Vol 268 (2) ◽

pp. 1132-1140

Author(s):

Y. Fukami ◽

K. Sato ◽

K. Ikeda ◽

K. Kamisango ◽

K. Koizumi ◽

...

Keyword(s):

Gene Product ◽

Src Homology 2 ◽

Src Gene ◽

Src Homology ◽

Src Homology 2 Domain ◽

Autophosphorylation Site

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Investigating the reason for loss-of-function of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) caused by Y279C mutation through molecular dynamics simulation

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2019.1634641 ◽

2019 ◽

Vol 38 (9) ◽

pp. 2509-2520 ◽

Cited By ~ 2

Author(s):

Wen-Shan Liu ◽

Rui-Rui Wang ◽

Wei-Ya Li ◽

Mei Rong ◽

Chi-Lu Liu ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Dynamics Simulation ◽

Loss Of Function ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain

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IL-6 blocks a discrete early step in lymphopoiesis

Blood ◽

10.1182/blood-2005-02-0456 ◽

2005 ◽

Vol 106 (3) ◽

pp. 879-885 ◽

Cited By ~ 48

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.

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