Shf, a Shb-like Adapter Protein, Is Involved in PDGF-α-Receptor Regulation of Apoptosis

Lindholm, Cecilia; Frantz, J. Daniel; Shoelson, Steven E.; Welsh, Michael

doi:10.1006/bbrc.2000.3847

Cited by 28 publications

(29 citation statements)

References 10 publications

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“…The downstream effects of these proteins have not been fully characterized; however, there is evidence to suggest that SHP-2 may be involved in feedback inhibition of the receptor (31), Crk may be important for cell migration (reviewed in ref. 32), and Shf may play a role in the regulation of apoptosis (29). In our assay, we found that iPDGFR␣-F720 and iPDGFR␣-F762 can restore mesoderm cell survival to PDGFR␣ blocked embryos.…”

Section: Pdgfr␣ Signaling Through Plc␥ and Pi3k But Not Shp-2 Shf Amentioning

confidence: 53%

“…There is also evidence to suggest that Shf may have a protective role in apoptosis. Overexpression of Shf in mouse fibroblasts prevents serum starvation-induced death, but the role of Shf in this process is unclear (29).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to Src kinases, PI3K, and PLC␥, the PDGFR␣ also binds the protein tyrosine phosphatase SHP-2 (Y720) (28) and the adaptor proteins Shf (Y720) (29) and Crk (Y762) (30). The downstream effects of these proteins have not been fully characterized; however, there is evidence to suggest that SHP-2 may be involved in feedback inhibition of the receptor (31), Crk may be important for cell migration (reviewed in ref.…”

Section: Pdgfr␣ Signaling Through Plc␥ and Pi3k But Not Shp-2 Shf Amentioning

confidence: 99%

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Distinct effectors of platelet-derived growth factor receptor-α signaling are required for cell survival during embryogenesis

Stry

Kazlauskas

Schreiber

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFR␣ or PDGFR␤ is embryonic lethal. In Xenopus embryos, disruption of PDGFR␣ signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFR␣ function in this process, we have analyzed all known effectorbinding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFR␣s, we have identified a role for phospholipase C␥ (PLC␥) in protecting cells from death. PDGFR␣-mediated cell survival requires PLC␥ and phosphatidylinositol 3-kinase signaling, and that PDGFR␣ with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFR␣ signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFR␣ signaling through PLC␥ and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos.apoptosis ͉ gastrulation ͉ phospholipase C␥ ͉ Xenopus

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Section: Pdgfr␣ Signaling Through Plc␥ and Pi3k But Not Shp-2 Shf Amentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Pdgfr␣ Signaling Through Plc␥ and Pi3k But Not Shp-2 Shf Amentioning

confidence: 99%

See 1 more Smart Citation

Distinct effectors of platelet-derived growth factor receptor-α signaling are required for cell survival during embryogenesis

Stry

Kazlauskas

Schreiber

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…SHB has three paralogues: SHD, SHE and SHF (Oda et al 1997, Lindholm et al 2000. They all share sequence similarity in the C-terminus and at the phosphorylation sites.…”

Section: Introductionmentioning

confidence: 99%

The role of the Src Homology-2 domain containing protein B (SHB) in β cells

Welsh

Jamalpour

Zang

et al. 2015

Journal of Molecular Endocrinology

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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 b 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 of Shb in 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, b 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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“…Since focal adhesion kinase (FAK) has been shown to regulate Rac activity [12], this signaling intermediate may also be of significance in this context. Shb is a widely expressed Src homology-2 domain containing adaptor protein [13,14] established as a regulator of reproduction [15], glucose homeostasis [16], angiogenesis [17] and T cell function [14,18,19]. Notably, Shb has also been found to regulate the cell cycle in the pancreas and blood system in a cell type dependent manner.…”

Section: Introductionmentioning

confidence: 99%

The Src homology 2 protein Shb promotes cell cycle progression in murine hematopoietic stem cells by regulation of focal adhesion kinase activity

Gustafsson¹,

Heffner²,

Wenzel³

et al. 2013

Experimental Cell Research

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The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb's known interaction partners are established regulators of blood cell development and function.In addition, Shb deficient embryonic stem cells displayed reduced blood cell colony formation upon differentiation in vitro. The aim of the current study was therefore to explore

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Shf, a Shb-like Adapter Protein, Is Involved in PDGF-α-Receptor Regulation of Apoptosis

Cited by 28 publications

References 10 publications

Distinct effectors of platelet-derived growth factor receptor-α signaling are required for cell survival during embryogenesis

Distinct effectors of platelet-derived growth factor receptor-α signaling are required for cell survival during embryogenesis

The role of the Src Homology-2 domain containing protein B (SHB) in β cells

The Src homology 2 protein Shb promotes cell cycle progression in murine hematopoietic stem cells by regulation of focal adhesion kinase activity

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