Toxoplasma gondii expresses two mitogen-activated protein kinase genes that represent distinct protozoan subfamilies

Michelle R. Lacey, Michael J. Brumlik, Rachael E. Yenni, Matthew E. Burow, Tyler J Curiel

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

All eukaryotes express mitogen-activated protein kinases (MAPKs) that govern diverse cellular processes including proliferation, differentiation, and survival. Even though these proteins are highly conserved throughout nature, MAPKs from closely related species often possess distinct signature sequences, making them well suited as drug discovery targets. Based on the central amino acid in the TXY dual phosphorylation loop, mammalian MAPKs are classified as extracellular signal-regulated kinases (ERKs), c-Jun amino-terminal kinases (JNKs), or p38 stress-response MAPKs. The presence of MAPKs in nonmetazoan eukaryotes suggests significant evolutionary conservation of these important signalling pathways. We recently cloned a novel stress-response MAPK gene (tgMAPK1) from Toxoplasma gondii, an obligate intracellular human parasite that can cause life-threatening infections in immunocompromised patients, and we now present data on a second T. gondii MAPK gene (tgMAPK2) that we cloned. We show that tgMAPK1 and tgMAPK2 are members of two distinct and previously unknown protozoan MAPK subfamilies that we have named pzMAPKl/pzMAPK3 and pzMAPK2. Our phylogenetic analysis of a collection of protozoan and metazoan MAPK genes in relation to ERK8-like genes demonstrates that an ERK8-like family, which includes the pzMAPK2 subfamily, is represented across a large variety of eukaryotic kingdoms and is evolutionarily very distant from other MAPK families.

Original languageEnglish (US)
Pages (from-to)4-14
Number of pages11
JournalJournal of Molecular Evolution
Volume64
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Toxoplasma
Toxoplasma gondii
Mitogen-Activated Protein Kinases
mitogen-activated protein kinase
Protozoa
Genes
protein
gene
genes
Eukaryota
eukaryote
eukaryotic cells
stress response
MAP Kinase Kinase 4
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Immunocompromised Host
Drug Discovery
metazoan

Keywords

  • Extracellular signal-regulated kinase
  • Mitogen-activated protein kinase
  • Phylogeny
  • Protozoa
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Genetics
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Genetics(clinical)
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

Cite this

Toxoplasma gondii expresses two mitogen-activated protein kinase genes that represent distinct protozoan subfamilies. / Lacey, Michelle R.; Brumlik, Michael J.; Yenni, Rachael E.; Burow, Matthew E.; Curiel, Tyler J.

In: Journal of Molecular Evolution, Vol. 64, No. 1, 01.2007, p. 4-14.

Research output: Contribution to journalArticle

Lacey, Michelle R. ; Brumlik, Michael J. ; Yenni, Rachael E. ; Burow, Matthew E. ; Curiel, Tyler J. / Toxoplasma gondii expresses two mitogen-activated protein kinase genes that represent distinct protozoan subfamilies. In: Journal of Molecular Evolution. 2007 ; Vol. 64, No. 1. pp. 4-14.
@article{aa68daef65714d5197e12af0c31129a6,
title = "Toxoplasma gondii expresses two mitogen-activated protein kinase genes that represent distinct protozoan subfamilies",
abstract = "All eukaryotes express mitogen-activated protein kinases (MAPKs) that govern diverse cellular processes including proliferation, differentiation, and survival. Even though these proteins are highly conserved throughout nature, MAPKs from closely related species often possess distinct signature sequences, making them well suited as drug discovery targets. Based on the central amino acid in the TXY dual phosphorylation loop, mammalian MAPKs are classified as extracellular signal-regulated kinases (ERKs), c-Jun amino-terminal kinases (JNKs), or p38 stress-response MAPKs. The presence of MAPKs in nonmetazoan eukaryotes suggests significant evolutionary conservation of these important signalling pathways. We recently cloned a novel stress-response MAPK gene (tgMAPK1) from Toxoplasma gondii, an obligate intracellular human parasite that can cause life-threatening infections in immunocompromised patients, and we now present data on a second T. gondii MAPK gene (tgMAPK2) that we cloned. We show that tgMAPK1 and tgMAPK2 are members of two distinct and previously unknown protozoan MAPK subfamilies that we have named pzMAPKl/pzMAPK3 and pzMAPK2. Our phylogenetic analysis of a collection of protozoan and metazoan MAPK genes in relation to ERK8-like genes demonstrates that an ERK8-like family, which includes the pzMAPK2 subfamily, is represented across a large variety of eukaryotic kingdoms and is evolutionarily very distant from other MAPK families.",
keywords = "Extracellular signal-regulated kinase, Mitogen-activated protein kinase, Phylogeny, Protozoa, Toxoplasma gondii",
author = "Lacey, {Michelle R.} and Brumlik, {Michael J.} and Yenni, {Rachael E.} and Burow, {Matthew E.} and Curiel, {Tyler J}",
year = "2007",
month = "1",
doi = "10.1007/s00239-005-0197-x",
language = "English (US)",
volume = "64",
pages = "4--14",
journal = "Journal of Molecular Evolution",
issn = "0022-2844",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Toxoplasma gondii expresses two mitogen-activated protein kinase genes that represent distinct protozoan subfamilies

AU - Lacey, Michelle R.

AU - Brumlik, Michael J.

AU - Yenni, Rachael E.

AU - Burow, Matthew E.

AU - Curiel, Tyler J

PY - 2007/1

Y1 - 2007/1

N2 - All eukaryotes express mitogen-activated protein kinases (MAPKs) that govern diverse cellular processes including proliferation, differentiation, and survival. Even though these proteins are highly conserved throughout nature, MAPKs from closely related species often possess distinct signature sequences, making them well suited as drug discovery targets. Based on the central amino acid in the TXY dual phosphorylation loop, mammalian MAPKs are classified as extracellular signal-regulated kinases (ERKs), c-Jun amino-terminal kinases (JNKs), or p38 stress-response MAPKs. The presence of MAPKs in nonmetazoan eukaryotes suggests significant evolutionary conservation of these important signalling pathways. We recently cloned a novel stress-response MAPK gene (tgMAPK1) from Toxoplasma gondii, an obligate intracellular human parasite that can cause life-threatening infections in immunocompromised patients, and we now present data on a second T. gondii MAPK gene (tgMAPK2) that we cloned. We show that tgMAPK1 and tgMAPK2 are members of two distinct and previously unknown protozoan MAPK subfamilies that we have named pzMAPKl/pzMAPK3 and pzMAPK2. Our phylogenetic analysis of a collection of protozoan and metazoan MAPK genes in relation to ERK8-like genes demonstrates that an ERK8-like family, which includes the pzMAPK2 subfamily, is represented across a large variety of eukaryotic kingdoms and is evolutionarily very distant from other MAPK families.

AB - All eukaryotes express mitogen-activated protein kinases (MAPKs) that govern diverse cellular processes including proliferation, differentiation, and survival. Even though these proteins are highly conserved throughout nature, MAPKs from closely related species often possess distinct signature sequences, making them well suited as drug discovery targets. Based on the central amino acid in the TXY dual phosphorylation loop, mammalian MAPKs are classified as extracellular signal-regulated kinases (ERKs), c-Jun amino-terminal kinases (JNKs), or p38 stress-response MAPKs. The presence of MAPKs in nonmetazoan eukaryotes suggests significant evolutionary conservation of these important signalling pathways. We recently cloned a novel stress-response MAPK gene (tgMAPK1) from Toxoplasma gondii, an obligate intracellular human parasite that can cause life-threatening infections in immunocompromised patients, and we now present data on a second T. gondii MAPK gene (tgMAPK2) that we cloned. We show that tgMAPK1 and tgMAPK2 are members of two distinct and previously unknown protozoan MAPK subfamilies that we have named pzMAPKl/pzMAPK3 and pzMAPK2. Our phylogenetic analysis of a collection of protozoan and metazoan MAPK genes in relation to ERK8-like genes demonstrates that an ERK8-like family, which includes the pzMAPK2 subfamily, is represented across a large variety of eukaryotic kingdoms and is evolutionarily very distant from other MAPK families.

KW - Extracellular signal-regulated kinase

KW - Mitogen-activated protein kinase

KW - Phylogeny

KW - Protozoa

KW - Toxoplasma gondii

UR - http://www.scopus.com/inward/record.url?scp=33845883531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845883531&partnerID=8YFLogxK

U2 - 10.1007/s00239-005-0197-x

DO - 10.1007/s00239-005-0197-x

M3 - Article

C2 - 17160647

AN - SCOPUS:33845883531

VL - 64

SP - 4

EP - 14

JO - Journal of Molecular Evolution

JF - Journal of Molecular Evolution

SN - 0022-2844

IS - 1

ER -