Saturday, October 29, 2011

Molecular cloning and characterization of Mitogen-activated protein kinase 2 in Toxoplasma gondii

Cell Cycle. 2011 Oct 31;10(20). [Epub ahead of print]

Molecular cloning and characterization of Mitogen-activated protein kinase 2 in Toxoplasma gondii.

Huang H, Ma YF, Bao Y, Lee H, Lisanti MP, Tanowitz HB, Weiss LM.

SourceDepartment of Pathology; Albert Einstein College of Medicine; Bronx, NY USA.

Abstract
Toxoplasma gondii is an obligate intracellular protozoan that is both a human and animal pathogen. This Apicomplexan causes significant morbidity and mortality in immune competent and immune compromised hosts. In humans, the most common manifestations of T. gondii infections are chorioretinitis in congenital infection and encephalitis in immune compromised patients such as patients with advanced AIDS. Mitogen-activated protein kinase (MAPK) pathways are major signal transduction systems by which eukaryotic cells convert environmental cues to intracellular events such as proliferation and differentiation. We have identified a T. gondii homologue of the MAPK family that we have called TgMAPK2. Sequence analyses demonstrated TgMAPK2 has homology with lower eukaryotic ERK2, but has significant differences from mammalian ERK2. TgMAPK2 has an open reading frame of 2037 bp, 678 amino acids, and its molecular weight is 73.1 kDa. It contains the typical twelve sub-domains of a MAPK and has a TDY motif in the dual phosphorylation and activation subdomains. This suggests that TgMAPK2 may play an important role in stress response. Recombinant TgMAPK2 was catalytically active and was not inhibited by a human ERK2 inhibitor, FR180204. A partial TgMAPK2 lacking the ATP binding motifs, GxGxxGxV, was successfully regulated by a ligand-controlled destabilization domain (ddFKBP) expression vector system in T. gondii. Since TgMAPK2 is significantly different from its mammalian counterpart it may be useful as a drug target. This work establishes a foundation for further study for this unique kinase.

PMID:22030559[PubMed - as supplied by publisher]

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