New Insights into the p38γ and p38δ MAPK Pathways

Ana Risco,Ana Cuenda

doi:10.1155/2012/520289

Abstract

The mammalian p38 mitogen-activated protein kinases (MAPKs) family is composed of four members (p38α, p38β, p38γ, and p38δ), which are very similar in amino acid sequence but differ in their expression patterns. This suggests that they may have specific functions in different organs. In the last years most of the effort has been centred on the study of the function of the p38α isoform, which is widely referred to as p38 in the literature. However, the role that other p38 isoforms play in cellular functions and their implication in some of the pathological conditions have not been precisely defined so far. In this paper we highlight recent advances made in defining the functions of the two less studied alternative p38MAPKs, p38γ and p38δ. We describe that these p38MAPKs show similarities to the classical p38α isoform, although they may play central and distinct role in certain physiological and pathological processes.

Highlights

To preserve the homeostasis and health of the organism cells are constantly responding to changes in the physical and chemical properties of the environment by altering many of their cellular functions
We provide an overview of the less known p38MAPK isoforms, the p38γ and p38δ Mitogen Activated Protein Kinases (MAPKs) pathways, which are strongly activated by stress, and play important roles in tissue regeneration, differentiation, metabolic diseases, and cancer
Most of the studies to date have focused on the role of the p38α isoform and report the implication of this p38MAPK isoform in numerous biological and physiological processes

Summary

Introduction

To preserve the homeostasis and health of the organism cells are constantly responding to changes in the physical and chemical properties of the environment by altering many of their cellular functions. The activation of Mitogen Activated Protein Kinases (MAPKs) is involved in the transduction of most extracellular signals, and it is one of the major signal transduction mechanism by which the cell adapts to changes in the surrounding medium. The isoform p38α was identified in 1994 by four groups as a 38 kDa polypeptide that is activated in response to endotoxin treatment, cell stress, or cytokines [1]. Two to three years later, three additional isoforms were described: p38β [2,3,4], p38γ [5, 6], and p38δ [7, 8] These kinases share highly similar protein sequences; p38α and p38β are 75% identical, whereas p38γ and p38δ are 62% and 61% identical to p38α, respectively. We provide an overview of the less known p38MAPK isoforms, the p38γ and p38δ MAPK pathways, which are strongly activated by stress, and play important roles in tissue regeneration, differentiation, metabolic diseases, and cancer

General Features of p38γ and p38δ MAPKs

Regulation of p38γ and p38δ

Physiological Roles of p38γ and p38δ MAPK Pathways

Conclusion