Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling. / Vemulapalli, Vidyasiri; Chylek, Lily A.; Erickson, Alison; Pfeiffer, Anamarija; Gabriel, Khal Hentz; Larochelle, Jonathan; Subramanian, Kartik; Cao, Ruili; Stegmaier, Kimberly; Mohseni, Morvarid; Lamarche, Matthew J.; Acker, Michael G.; Sorger, Peter K.; Gygi, Steven P.; Blacklow, Stephen C.

In: eLife, Vol. 10, e64251, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Vemulapalli, V, Chylek, LA, Erickson, A, Pfeiffer, A, Gabriel, KH, Larochelle, J, Subramanian, K, Cao, R, Stegmaier, K, Mohseni, M, Lamarche, MJ, Acker, MG, Sorger, PK, Gygi, SP & Blacklow, SC 2021, 'Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling', eLife, vol. 10, e64251. https://doi.org/10.7554/eLife.64251

APA

Vemulapalli, V., Chylek, L. A., Erickson, A., Pfeiffer, A., Gabriel, K. H., Larochelle, J., Subramanian, K., Cao, R., Stegmaier, K., Mohseni, M., Lamarche, M. J., Acker, M. G., Sorger, P. K., Gygi, S. P., & Blacklow, S. C. (2021). Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling. eLife, 10, [e64251]. https://doi.org/10.7554/eLife.64251

Vancouver

Vemulapalli V, Chylek LA, Erickson A, Pfeiffer A, Gabriel KH, Larochelle J et al. Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling. eLife. 2021;10. e64251. https://doi.org/10.7554/eLife.64251

Author

Vemulapalli, Vidyasiri ; Chylek, Lily A. ; Erickson, Alison ; Pfeiffer, Anamarija ; Gabriel, Khal Hentz ; Larochelle, Jonathan ; Subramanian, Kartik ; Cao, Ruili ; Stegmaier, Kimberly ; Mohseni, Morvarid ; Lamarche, Matthew J. ; Acker, Michael G. ; Sorger, Peter K. ; Gygi, Steven P. ; Blacklow, Stephen C. / Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling. In: eLife. 2021 ; Vol. 10.

Bibtex

@article{a04f5d725c1a47328fb73d48a25c31be,
title = "Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling",
abstract = "SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines, yet is frequently mutated in human cancer. Here, we examine the role of SHP2 in the responses of breast cancer cells to EGF by monitoring phosphoproteome dynamics when SHP2 is allosterically inhibited by SHP099. The dynamics of phosphotyrosine abundance at more than 400 tyrosine residues reveal six distinct response signatures following SHP099 treatment and washout. Remarkably, in addition to newly identified substrate sites on proteins such as occludin, ARHGAP35, and PLCγ2, another class of sites shows reduced phosphotyrosine abundance upon SHP2 inhibition. Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. These findings highlight the distinct roles of the scaffolding and catalytic activities of SHP2 in effecting a transmembrane signaling response.",
author = "Vidyasiri Vemulapalli and Chylek, {Lily A.} and Alison Erickson and Anamarija Pfeiffer and Gabriel, {Khal Hentz} and Jonathan Larochelle and Kartik Subramanian and Ruili Cao and Kimberly Stegmaier and Morvarid Mohseni and Lamarche, {Matthew J.} and Acker, {Michael G.} and Sorger, {Peter K.} and Gygi, {Steven P.} and Blacklow, {Stephen C.}",
year = "2021",
doi = "10.7554/eLife.64251",
language = "English",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - Time resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of shp2-dependent signaling

AU - Vemulapalli, Vidyasiri

AU - Chylek, Lily A.

AU - Erickson, Alison

AU - Pfeiffer, Anamarija

AU - Gabriel, Khal Hentz

AU - Larochelle, Jonathan

AU - Subramanian, Kartik

AU - Cao, Ruili

AU - Stegmaier, Kimberly

AU - Mohseni, Morvarid

AU - Lamarche, Matthew J.

AU - Acker, Michael G.

AU - Sorger, Peter K.

AU - Gygi, Steven P.

AU - Blacklow, Stephen C.

PY - 2021

Y1 - 2021

N2 - SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines, yet is frequently mutated in human cancer. Here, we examine the role of SHP2 in the responses of breast cancer cells to EGF by monitoring phosphoproteome dynamics when SHP2 is allosterically inhibited by SHP099. The dynamics of phosphotyrosine abundance at more than 400 tyrosine residues reveal six distinct response signatures following SHP099 treatment and washout. Remarkably, in addition to newly identified substrate sites on proteins such as occludin, ARHGAP35, and PLCγ2, another class of sites shows reduced phosphotyrosine abundance upon SHP2 inhibition. Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. These findings highlight the distinct roles of the scaffolding and catalytic activities of SHP2 in effecting a transmembrane signaling response.

AB - SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines, yet is frequently mutated in human cancer. Here, we examine the role of SHP2 in the responses of breast cancer cells to EGF by monitoring phosphoproteome dynamics when SHP2 is allosterically inhibited by SHP099. The dynamics of phosphotyrosine abundance at more than 400 tyrosine residues reveal six distinct response signatures following SHP099 treatment and washout. Remarkably, in addition to newly identified substrate sites on proteins such as occludin, ARHGAP35, and PLCγ2, another class of sites shows reduced phosphotyrosine abundance upon SHP2 inhibition. Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. These findings highlight the distinct roles of the scaffolding and catalytic activities of SHP2 in effecting a transmembrane signaling response.

U2 - 10.7554/eLife.64251

DO - 10.7554/eLife.64251

M3 - Journal article

C2 - 33755016

AN - SCOPUS:85103331178

VL - 10

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e64251

ER -

ID: 261160922