The secretory pathway kinases

Biochim Biophys Acta. 2015 Oct;1854(10 Pt B):1687-93. doi: 10.1016/j.bbapap.2015.03.015. Epub 2015 Apr 8.

Abstract

Protein phosphorylation is a nearly universal post-translation modification involved in a plethora of cellular events. Even though phosphorylation of extracellular proteins had been observed, the identity of the kinases that phosphorylate secreted proteins remained a mystery until only recently. Advances in genome sequencing and genetic studies have paved the way for the discovery of a new class of kinases that localize within the endoplasmic reticulum, Golgi apparatus and the extracellular space. These novel kinases phosphorylate proteins and proteoglycans in the secretory pathway and appear to regulate various extracellular processes. Mutations in these kinases cause human disease, thus underscoring the biological importance of phosphorylation within the secretory pathway. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.

Keywords: Fam20C; Kinases; Raine syndrome; Secretory pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Abnormalities, Multiple / enzymology
  • Abnormalities, Multiple / genetics*
  • Animals
  • Casein Kinase I / chemistry
  • Casein Kinase I / genetics*
  • Casein Kinase I / metabolism
  • Cleft Palate / enzymology
  • Cleft Palate / genetics*
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / genetics
  • Exophthalmos / enzymology
  • Exophthalmos / genetics*
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Golgi Apparatus / enzymology
  • Golgi Apparatus / genetics
  • Humans
  • Microcephaly / enzymology
  • Microcephaly / genetics*
  • Mutation
  • Osteosclerosis / enzymology
  • Osteosclerosis / genetics*
  • Phosphorylation / genetics
  • Protein Conformation
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Secretory Pathway / genetics*
  • Substrate Specificity

Substances

  • Extracellular Matrix Proteins
  • Protein-Tyrosine Kinases
  • VLK protein, human
  • Casein Kinase I
  • FAM20C protein, human

Supplementary concepts

  • Raine syndrome