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. 2012 May 29;17(3):422–432. doi: 10.2478/s11658-012-0020-9

SHP-2 and PTP-pest induction during Rb-E2F associated apoptosis

Liza D Morales 1,3, Karina Pena 1, Dae Joon Kim 2,3, Jonathan H Lieman 1,✉
PMCID: PMC6275625  PMID: 22644489

Abstract

Apoptosis is intimately connected to cell cycle regulation via the Retinoblastoma (Rb)-E2F pathway and thereby serves an essential role in tumor suppression by eliminating aberrant hyperproliferative cells. Upon loss of Rb activity, an apoptotic response can be elicited through both p53-dependent and p53-independent mechanisms. While much of this apoptotic response has been attributed to the p19ARF/p53 pathway, increasing evidence has supported the role of protein tyrosine phosphatases (PTPs) in contributing to the initiation of the Rb-E2F-associated apoptotic response. One protein tyrosine phosphatase, PTP-1B, which is induced by the Rb-E2F pathway, has been shown to contribute to a p53-independent apoptotic pathway by inactivating focal adhesion kinase. This report identifies two additional PTPs, SHP-2 and PTP-PEST, that are also directly activated by the Rb-E2F pathway and which can contribute to signal transduction during p53-independent apoptosis.

Key words: Apoptosis, Focal adhesion kinase, Rb, E2F-1, Phosphatase, PTP-1B, SHP-2, PTP-PEST, PTPN1, PTPN11, PTPN12, Tumor suppressor

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Abbreviations used

4OHT

4-hydroxytamoxifen

dnE2F

dominant negative mutant of E2F-1

ER

estrogen receptor

FAK

focal adhesion kinase

PTP

protein tyrosine phosphatase

PTP-PEST

protein tyrosine phosphatase rich in proline, glutamic acid/aspartic acid, and serine/threonine residues

Rb

retinoblastoma protein

SHP-2

SH2 domain-containing tyrosine phosphatase

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