Novel Functions of Death-Associated Protein Kinases through Mitogen-Activated Protein Kinase-Related Signals.

Mohamed Elbadawy,Kazuaki Sasaki,Tatsuya Usui,Hideyuki Yamawaki

doi:10.3390/ijms19103031

Abstract

Death associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine kinase; its main function is to regulate cell death. DAPK family proteins consist of DAPK1, DAPK2, DAPK3, DAPK-related apoptosis-inducing protein kinases (DRAK)-1 and DRAK-2. In this review, we discuss the roles and regulatory mechanisms of DAPK family members and their relevance to diseases. Furthermore, a special focus is given to several reports describing cross-talks between DAPKs and mitogen-activated protein kinases (MAPK) family members in various pathologies. We also discuss small molecule inhibitors of DAPKs and their potential as therapeutic targets against human diseases.

Highlights

Death associated protein kinase (DAPK), mitogen-activated protein kinases (MAPK)Death-associated protein kinase (DAPK) family proteins are closely related, Ca2+/calmodulin (CaM)-regulated serine/threonine kinases, whose members possess significant homology in their catalytic domains and share cell death-associated functions [1,2]
MAPKs mediate signal transduction pathways that are involved in cellular responses to a diverse range of stimuli, such as mitogens, hormones, osmotic stress, heat shock, proinflammatory cytokines, and significant developmental changes in organisms
We introduce the reports showing the regulatory mechanisms and various functions of DAPK family proteins

Summary

Introduction

Death-associated protein kinase (DAPK) family proteins are closely related, Ca2+/calmodulin (CaM)-regulated serine/threonine kinases, whose members possess significant homology in their catalytic domains and share cell death-associated functions [1,2]. MAPKs mediate signal transduction pathways that are involved in cellular responses to a diverse range of stimuli, such as mitogens, hormones, osmotic stress, heat shock, proinflammatory cytokines, and significant developmental changes in organisms. They mediate cellular functions including proliferation, differentiation, mitosis, gene expression, and apoptosis [11]. We refer to reports indicating the relationship between DAPK and MAPK family proteins in multiple diseases

Cellular Functions of DAPK Family Proteins

Regulation of DAPK Family Proteins

DAPKs in Disease

Cross-Talk between DAPKs and ERK Signaling

Conclusions