The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for activation of the mitogen-activated protein kinase cascade in a B-cell line

Kumar, Gita; Wang, S.; Gupta, Shalini; Nel, André E.

doi:10.1042/bj3070215

Cited by 27 publications

(13 citation statements)

References 47 publications

(68 reference statements)

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“…Grb2 and SOS could then bind to membrane-bound Shc rather than directly to the receptor. Indeed, BCR cross-linking leads to the tyrosine phosphorylation of Shc in a Syk-dependent manner (37,44) and to the assembly of a Shc-Grb2-SOS complex, although it is unclear how this complex associates with the plasma membrane (24,27,48,49).…”

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confidence: 99%

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Shc Contains Two Grb2 Binding Sites Needed for Efficient Formation of Complexes with SOS in B Lymphocytes

Harmer

DeFranco

1997

Molecular and Cellular Biology

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Cross-linking of the B-cell antigen receptor (BCR) induces tyrosine phosphorylation of Shc, which is believed to lead to the activation of Ras. Previous work has shown that tyrosine-phosphorylated Shc forms complexes with another adapter protein, Grb2, and the Ras guanine nucleotide exchange factor SOS. Here, we demonstrate that phosphorylation of Shc by the hematopoietic cell-specific tyrosine kinase Syk induces binding of Grb2 to Shc, suggesting that Syk phosphorylates Shc in stimulated B cells. Surprisingly, Syk-phosphorylated Shc possesses two Grb2 binding sites rather than the one site that has been previously reported. Both of these sites are required for efficient formation of Shc-Grb2-SOS complexes in vitro and in vivo. We suggest that two Grb2 proteins anchored by a single Shc protein bind simultaneously to one SOS molecule, resulting in a complex that is more stable than a complex containing only a single Grb2 protein bound to one SOS molecule. This model is consistent with our observation that BCR stimulation greatly increases the amount of SOS associated with Grb2.

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confidence: 99%

“…Among the many proteins that are tyrosine phosphorylated upon BCR cross-linking is the adapter protein Shc (24,27,48,49). B lymphocytes express two Shc isoforms, of 46 and 52 kDa, which are the products of a single mRNA translationally initiated at two different sites (41).…”

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confidence: 99%

Shc Contains Two Grb2 Binding Sites Needed for Efficient Formation of Complexes with SOS in B Lymphocytes

Harmer

DeFranco

1997

Molecular and Cellular Biology

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“…Raf activates MAP kinase kinase, MAPK/ERK kinase, which in turn phosphorylates and activates microtubuleassociated kinases, MAPK (or extracellular signal regulated kinases, ERK). Activated MAPK then phosphorylates several intracellular substrates on Ser/Thr residues, such as other Ser/Thr kinases, cytoskeletal proteins, or transcription factors (15,16).…”

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confidence: 99%

Human Type II Fcγ Receptors Inhibit B Cell Activation by Interacting with the p21 -dependent Pathway

Sármay¹,

Koncz

Gergely

1996

Journal of Biological Chemistry

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“…6B). As reported for the other cell types, Grb2 and Sos formed a constitutive complex in IL-1␤-activated HUVEC (23)(24)(25) (Fig. 6C).…”

Section: Shp2 Associated With E-selectin Is Enzymatically Active and mentioning

confidence: 55%

“…It has been described that Sos, a guanine nucleotide-releasing factor, can recruit Ras to the cytoplasmic membrane to carry out Ras/Raf-1/MEK signaling (20,25). To determine whether the events we describe above were related to Ras, we immunoprecipitated Sos from total HUVEC cell lysates and immunoblotted for Ras (Fig.…”

Section: Shp2 Associated With E-selectin Is Enzymatically Active and mentioning

confidence: 99%

Molecular Events in Transmembrane Signaling via E-selectin

Szente

Kíely

et al. 2001

Journal of Biological Chemistry

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E-selectin is a cytokine-inducible adhesion molecule that is expressed by activated endothelial cells at sites of inflammation. In addition to supporting rolling and stable arrest of leukocytes, there is increasing evidence that E-selectin functions in transmembrane signaling into endothelial cells during these adhesive interactions. We have previously shown that adhesion of HL-60 cells (which express ligands for E-selectin), or antibodymediated cross-linking of E-selectin, results in formation of a Ras/Raf-1/phospho-MEK macrocomplex, extracellular signal-regulated protein kinase (ERK1/2) activation, and c-fos up-regulation. All of these downstream signaling events appear to require an intact cytoplasmic domain of E-selectin. Here we demonstrate that tyrosine 603 in the cytoplasmic domain of E-selectin is required for the E-selectin-dependent ERK1/2 activation. Tyrosine 603 plays an important role in mediating the association of E-selectin with SHP2, and the catalytic domain of SHP2 is, in turn, critical for E-selectin-dependent ERK1/2 activation. An adapter protein complex consisting of Shc⅐Grb2⅐Sos bridges between SHP2 and the Ras⅐Raf⅐phospho-MEK macrocomplex. These molecular events thus outline a mechanism by which cross-linking of E-selectin by engagement of ligands on adherent leukocytes can initiate a multifunctional signaling pathway in the activated endothelial cell at sites of inflammation. E-selectin is an inducible adhesion molecule that is expressed at relatively high density on the surface of cultured endothelial cells that have been activated by proinflammatory cytokines, such as interleukin-1b (IL-1␤), 1 tumor necrosis factor-␣, or bacterial endotoxin. It is detectable in vivo at the sites of inflammation (1-3). In addition to supporting the rolling and stable arrest of leukocytes on activated endothelium, there is increasing evidence that E-selectin can transduce outside-in signals (4 -6). Recently our laboratory demonstrated that leukocyte adhesion to cell surface E-selectin-activated extracellular signal-regulated protein kinase (ERK1/2), formed a macrocomplex containing Ras/Raf-1/phospho-MEK, and resulted in the up-regulation of c-fos expression (7). In this study, we have investigated the molecular events occurring immediately upstream of Ras/Raf/phospho-MEK and downstream of cell surface E-selectin. The cytoplasmic domain of E-selectin has been implicated in transmembrane signaling (5, 7); however, the molecular mechanisms involved have not been well defined. The cytoplasmic domain of E-selectin consists of 32 amino acids (1), including two tyrosine residues. It has been well documented that phosphorylation of tyrosine residues in the cytoplasmic domains of various types of receptors can play an important role in receptor-mediated transmembrane signal transduction, especially ERK1/2 activation. Therefore, it is reasonable to hypothesize that the two tyrosine residues on the cytoplasmic domain of E-selectin may be involved in the E-selectin-dependent ERK1/2 activation described by our laborat...

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The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for activation of the mitogen-activated protein kinase cascade in a B-cell line

Cited by 27 publications

References 47 publications

Shc Contains Two Grb2 Binding Sites Needed for Efficient Formation of Complexes with SOS in B Lymphocytes

Shc Contains Two Grb2 Binding Sites Needed for Efficient Formation of Complexes with SOS in B Lymphocytes

Human Type II Fcγ Receptors Inhibit B Cell Activation by Interacting with the p21 -dependent Pathway

Molecular Events in Transmembrane Signaling via E-selectin

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