Cancer and Metastasis Reviews

, Volume 27, Issue 2, pp 179–192

The tyrosine phosphatase Shp2 (PTPN11) in cancer

  • Gordon Chan
  • Demetrios Kalaitzidis
  • Benjamin G. Neel
Article

Abstract

Diverse cellular processes are regulated by tyrosyl phosphorylation, which is controlled by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). De-regulated tyrosyl phosphorylation, evoked by gain-of-function mutations and/or over-expression of PTKs, contributes to the pathogenesis of many cancers and other human diseases. PTPs, because they oppose the action of PTKs, had been considered to be prime suspects for potential tumor suppressor genes. Surprisingly, few, if any, tumor suppressor PTPs have been identified. However, the Src homology-2 domain-containing phosphatase Shp2 (encoded by PTPN11) is a bona fide proto-oncogene. Germline mutations in PTPN11 cause Noonan and LEOPARD syndromes, whereas somatic PTPN11 mutations occur in several types of hematologic malignancies, most notably juvenile myelomonocytic leukemia and, more rarely, in solid tumors. Shp2 also is an essential component in several other oncogene signaling pathways. Elucidation of the events underlying Shp2-evoked transformation may provide new insights into oncogenic mechanisms and novel targets for anti-cancer therapy.

Keywords

Shp2 Shp-2 PTPN11 Protein-tyrosine phosphatase (PTP) Leukemia Juvenile myelomonocytic leukemia (JMML) Noonan syndrome Cancer Signal transduction Helicobacter pylori Breast cancer 

Abbreviations

AGM

aorta-gonad-mesonephros

ALCL

anaplastic large cell lymphoma

AML

acute myelogenous leukemia

B-ALL

B-acute lymphoblastic leukemia

BM

bone marrow

BMMs

bone marrow macrophages

CagA

cytoxin-associated antigen A

CFU

colony forming unit

CML

chronic myelogenous leukemia

CMML

chronic myelomonocytic leukemia

FL

fetal liver

FRS

fibroblast growth factor receptor substrate

GAB

GRB2-associated binders

ICSBP

interferon consensus sequence binding protein

IRF8

interferon response factor 8

IRS

insulin receptor substrate

JMML

juvenile myelomonocytic leukemia

LS

LEOPARD syndrome

MDS

myelodysplastic syndrome

MM

multiple myeloma

MPD

myeloproliferative disease

NS

Noonan syndrome

NRPTPs

non-receptor PTPs

PTKs

protein-tyrosine kinases

PTPs

protein-tyrosine phosphatases

pY

Phosphotyrosyl

RTKs

receptor tyrosine kinases

SFK

Src family kinase

SH2

Src homology-2

WT

wild type

YS

yolk sac

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gordon Chan
    • 1
  • Demetrios Kalaitzidis
    • 2
  • Benjamin G. Neel
    • 1
  1. 1.Ontario Cancer InstituteTorontoCanada
  2. 2.Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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