Mitogen activated protein kinase phosphatases and cancer

Abstract

Deregulation of cell signaling is a vital part of cancer development. The mitogen activated protein kinase (MAPK) family is involved in regulating both cell growth and cell death. This family of kinases is negatively regulated by mitogen activated protein kinase phosphatases (MKPs). MKPs are dual specificity phosphatases that target threonine and tyrosine residues that appear in a TXY motif. There are eleven members of the MKP family. Expression of MKPs has been shown to be altered in many different types of cancer. Most of what is known centers on MKP-1, MKP-2 and MKP-3. This review will focus on their role in cancer development and progression.

Figure 1

Regulation of MAP kinase signaling by MKP-1, MKP-2 and MKP-3. Cell signals are received at the plasma membrane and transmitted through the MAP kinase signaling cascade. Each MAPK family member has its own specific MKKKs and MKKs. MKP dephosphorylation attenuates MAP Kinase activity. ERK, JNK and p38 are dephosphorylated by MKP-1 and MKP-2. MKP-3 dephosphorylates ERK. The other MKP family members also regulate MAPKs by dephosphorylation. MKP-1, MKP-2 and MKP-3 are shown here because their activity is the main focus of this review.