Receptor-Specific Regulation of Phosphatidylinositol 3′-Kinase Activation by the Protein Tyrosine Phosphatase Shp2

Zhang, Si Qing; Tsiaras, William G.; Araki, Toshiyuki; Wen, Gengyun; Minichiello, Liliana; Klein, Rüdiger; Neel, Benjamin G.

doi:10.1128/mcb.22.12.4062-4072.2002

Cited by 243 publications

(240 citation statements)

References 49 publications

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“…We thus determined if LS mutations had the same effect on SHP-2 catalytic activity when assayed on a validated SHP-2 substrate. To this aim, we designed a phosphopeptide encompassing Y589 of Gab1 (Gab1-pY589 phosphopeptide), which corresponds to a PI3K-binding site and is known to be dephosphorylated by SHP-2 in cells treated with EGF [6]. As shown in Fig.…”

Section: Ptp Assay Of Ls Mutants Using a Specific Shp-2 Substratementioning

confidence: 99%

“…Because SHP-2 can dephosphorylate Gab1 on its PI3K-binding sites in response to EGF [6], we designed an experiment to monitor these sites phosphorylation. Vero cells were chosen again, since they can be efficiently stimulated by EGF, leading to the phosphorylation of Gab1 and the downstream activation of SHP-2 and PI3K [5,13].…”

Section: 4mentioning

confidence: 99%

“…Besides this signal-enhancing function, SHP-2 can play a modulatory role in the activation of phosphoinositide 3-kinase (PI3K), at least downstream of the EGF receptor. Indeed, this receptor recruits PI3K by phosphorylating Gab1 on binding sites for p85, the regulatory subunit of PI3K, and it was recently shown that these sites are dephosphorylated by SHP-2 during EGF stimulation [6].…”

Section: Introductionmentioning

confidence: 99%

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Reduced phosphatase activity of SHP‐2 in LEOPARD syndrome: Consequences for PI3K binding on Gab1

et al. 2006

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LEOPARD (LS) and Noonan (NS) are overlapping syndromes associated with distinct mutations of SHP-2. Whereas NS mutations enhance SHP-2 catalytic activity, we show that the activity of three representative LS mutants is undetectable when assayed using a standard protein tyrosine phosphatase (PTP) substrate. A different assay using a specific SHP-2 substrate confirms their decreased PTP activity, but also reveals a significant activity of the T468M mutant. In transfected cells stimulated with epidermal growth factor, the least active LS mutants promote Gab1/PI3K binding, validating our in vitro data. LS mutants thus display a reduced PTP activity both in vitro and in transfected cells.

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Section: Ptp Assay Of Ls Mutants Using a Specific Shp-2 Substratementioning

confidence: 99%

Section: 4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reduced phosphatase activity of SHP‐2 in LEOPARD syndrome: Consequences for PI3K binding on Gab1

et al. 2006

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“…The role of SHP-2 phosphatase in growth factor-induced PI3 kinase pathways varies, depending on the stimulus and its intracellular signaling mechanisms. SHP-2 plays negative or positive roles in EGF and IGF-1-induced PI3 kinase activation, respectively, while PDGF-induced PI3 kinase activation was not affected by loss of SHP-2 function (Zhang et al, 2002). We provide evidence in this report that in IL-3 signaling, although phosphatase activity of SHP-2 was redundant for PI3 kinase activation, an intact SHP-2 protein was indeed required (Figure 3c), suggesting that SHP-2 facilitates IL-3-induced PI3 kinase activation as an adaptor protein.…”

Section: Derivation Of Immortalized Shp-2 à/à Hematopoietic Cell Poolsmentioning

confidence: 99%

Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling

Hawley

et al. 2003

Oncogene

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“…SHP2 binds to several RTK [2,3], adaptor proteins [4][5][6][7][8][9][10][11][12], and SHPS-1 [13]. These interactions are essential for growth factor-or cytokine-induced activation of the multiple receptor-evoked functions.…”

Section: Introductionmentioning

confidence: 99%

Annexin II binds to SHP2 and this interaction is regulated by HSP70 levels

Yoo

Hayman

2007

Biochemical and Biophysical Research Communications

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The protein tyrosine phosphatase SHP2 is a positive effector of EGFR signaling. To improve our understanding of SHP2's function, we searched for additional binding proteins of SHP2. We found that Annexin II is an SHP2 binding protein. Physical interactions of SHP2 with Annexin II were confirmed in vivo. Furthermore, binding of SHP2 with Annexin II was regulated somewhat by EGF treatment and the extracellular Ca 2+ chelator, EGTA. Previously, we reported that HSP70 levels can influence the binding of SHP2 with EGFR. Interestingly, increased HSP70 levels also inhibited the binding of SHP2 with Annexin II after EGF treatment in vivo. In addition, immunostaining experiments indicated that a fraction of SHP2 and Annexin II co-localized in the cell membrane region after EGF treatment. Our findings indicate that Annexin II is binding partner of SHP2 and the binding of SHP2 with Annexin II is affected by EGF stimulation, extracellular calcium levels and the levels of HSP70.

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Receptor-Specific Regulation of Phosphatidylinositol 3′-Kinase Activation by the Protein Tyrosine Phosphatase Shp2

Cited by 243 publications

References 49 publications

Reduced phosphatase activity of SHP‐2 in LEOPARD syndrome: Consequences for PI3K binding on Gab1

Reduced phosphatase activity of SHP‐2 in LEOPARD syndrome: Consequences for PI3K binding on Gab1

Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling

Annexin II binds to SHP2 and this interaction is regulated by HSP70 levels

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