Proteomic database mining opens up avenues utilizing extracellular protein phosphorylation for novel therapeutic applications.

Garif Yalak,Bjorn R Olsen

doi:10.1186/s12967-015-0482-4

Abstract

SummaryRecent advances in extracellular signaling suggest that extracellular protein phosphorylation is a regulatory mechanism outside the cell. The list of reported active extracellular protein kinases and phosphatases is growing, and phosphorylation of an increasing number of extracellular matrix molecules and extracellular domains of trans-membrane proteins is being documented. Here, we use public proteomic databases, collagens – the major components of the extracellular matrix, extracellular signaling molecules and proteolytic enzymes as examples to assess what the roles of extracellular protein phosphorylation may be in health and disease. We propose that novel tools be developed to help assess the role of extracellular protein phosphorylation and translate the findings for biomedical applications. Furthermore, we suggest that the phosphorylation state of extracellular matrix components as well as the presence of extracellular kinases be taken into account when designing translational medical applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0482-4) contains supplementary material, which is available to authorized users.

Highlights

Technical advances have significantly contributed to insights into the functional role of extracellular protein phosphorylation
As shown in the example of collagens, several functions of extracellular matrix components may be regulated by extracellular protein phosphorylation
With the facts indicating that most collagen types, MMPs and bone morphogenetic proteins (BMPs) can occur in both phosphorylated and nonphosphorylated forms, we believe that phosphorylation may well represent a mechanism for regulating their functions

Summary

Recent advances in extracellular signaling suggest that extracellular protein phosphorylation is a regulatory mechanism outside the cell. The list of reported active extracellular protein kinases and phosphatases is growing, and phosphorylation of an increasing number of extracellular matrix molecules and extracellular domains of trans-membrane proteins is being documented. We use public proteomic databases, collagens – the major components of the extracellular matrix, extracellular signaling molecules and proteolytic enzymes as examples to assess what the roles of extracellular protein phosphorylation may be in health and disease. We propose that novel tools be developed to help assess the role of extracellular protein phosphorylation and translate the findings for biomedical applications. We suggest that the phosphorylation state of extracellular matrix components as well as the presence of extracellular kinases be taken into account when designing translational medical applications

Introduction

Findings

Conclusion