Crystal structure of the cGMP-dependent protein kinase II leucine zipper and Rab11b protein complex reveals molecular details of G-kinase-specific interactions.

cGMP-dependent protein kinase (PKG)-interacting proteins (GKIPs) mediate cellular targeting of PKG isoforms by interacting with their leucine zipper (LZ) domains. These interactions prevent aberrant signaling cross-talk between different PKG isotypes. To gain detailed insight into isotype-specific GKIP recognition by PKG, we analyzed the type II PKG leucine zipper domain and found that residues 40-83 dimerized and specifically interacted with Rab11b.

PCTAIRE kinase 3/cyclin-dependent kinase 18 is activated through association with cyclin A and/or phosphorylation by protein kinase A.

PCTAIRE kinase 3 (PCTK3)/cyclin-dependent kinase 18 (CDK18) is an uncharacterized member of the CDK family because its activator(s) remains unidentified. Here we describe the mechanisms of catalytic activation of PCTK3 by cyclin A2 and cAMP-dependent protein kinase (PKA). Using a pulldown experiment with HEK293T cells, cyclin A2 and cyclin E1 were identified as proteins that interacted with PCTK3.

Verification of protein disulfide bond arrangement by in-gel tryptic digestion under entirely neutral pH conditions.

To develop a concise proteomic procedure to verify the protein disulfide bond arrangement, non-reductive trypsin digestion of neuregulin 1-beta1 (176-246), a model disulfide-containing protein, was assessed by a proteolytic (18)O-labeling analysis. As a result, the commonly used in-gel tryptic digestion method has been improved for use entirely under neutral pH conditions. With this procedure, the disulfide arrangement of proteins could represent a clinical index candidate in pathological proteomic studies.

Fmoc-based solid phase chemical synthesis of 71-meric neuregulin 1-beta1, an epidermal growth factor-like domain.

The human neuregulin 1-beta1 (NRG1-beta1, amino acid residues 176-246) was chemically synthesized by Fmoc-based solid phase peptide synthesis (SPPS) followed by folding in a redox buffer. The biological activity of the synthesized NRG1-beta1 was confirmed by ligand-induced tyrosine phosphorylation on Chinese hamster ovary (CHO) cells expressing ErbB-4.

DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy.

DJ-1 plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of Parkinson's disease. DJ-1 has a protease-like structure and transthyretin (TTR), a protein causing familial amyloidotic polyneuropathy (FAP), was identified as a substrate for DJ-1 protease in this study. Both TTR and DJ-1 were secreted into the culture medium under normal conditions, and secreted TTR was not aggregated.

PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model.

DJ-1 has recently been shown to be responsible for onset of familial Parkinson's disease (PD), PARK7. DJ-1 has been shown to play roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD. In this study, a recombinant DJ-1 protein was administrated into the brain of PD model rats that had been injected to 6-hydroxydopamine (6-OHDA) in the left substantia nigra.

DJ-1 interacts with HIPK1 and affects H2O2-induced cell death.

DJ-1 is a novel oncogene and causative gene for the familial form of Parkinson's disease (PD). DJ-1 has multiple functions, including anti-oxidative stress by eliminating reactive oxygen species (ROS) and transcriptional regulation as a coactivator, and loss of these functions are thought to trigger the onset of PD. The mechanism underlying the prevention of cell death by DJ-1 is, however, not clear.