Source:http://linkedlifedata.com/resource/pubmed/id/14570876
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
52
|
| pubmed:dateCreated |
2003-12-22
|
| pubmed:abstractText |
Atypical protein kinase C iota/lambda (PKCiota/lambda) is essential for protein transport in the early secretory pathway. The small GTPase Rab2 selectively recruits the kinase to vesicular tubular clusters (VTCs) where PKCiota/lambda phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPDH). VTCs are composed of small vesicles and tubules and serve as transport intermediates that shuttle cargo from the endoplasmic reticulum to the Golgi complex. These structures are the first site of segregation of the anterograde and retrograde pathways. When Rab2 binds to a VTC subcompartment, the subsequent recruitment of PKCiota/lambda and soluble components, including COPI (coatomer and ADP-ribosylation factor), results in the release of retrograde-directed vesicles. Because Rab2 stimulates PKCiota/lambda membrane association in a dose-dependent manner, we investigated whether the two proteins physically interact. Using a combination of in vivo and in vitro assays, we found that Rab2 interacts directly with PKCiota/lambda and that this interaction occurs through the Rab2 amino terminus (residues 1-19) and the PKCiota/lambda regulatory domain. A mutant lacking the PKCiota/lambda binding domain (Rab2N'Delta19) was functionally characterized. In contrast to Rab2, Rab2N'Delta19 failed to recruit PKCiota/lambda to normal rat kidney microsomes in a quantitative binding assay. To determine whether Rab2 modulates the ability of PKCiota/lambda to phosphorylate GAPDH, an in vitro kinase assay was supplemented with Rab2 or Rab2N'Delta19. Rab2 inhibited PKCiota/lambda-dependent GAPDH phosphorylation, whereas no effect was observed when the assay was performed with the aminoterminal truncation mutant. These results suggest that a downstream effector recruited to the VTC stimulates PKCiota/lambda-mediated GAPDH phosphorylation by alleviating the inhibition imposed by Rab2-PKCiota/lambda interaction.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Coat Protein Complex I,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Glyceraldehyde-3-Phosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C lambda,
http://linkedlifedata.com/resource/pubmed/chemical/rab2 GTP-Binding Protein
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
26
|
| pubmed:volume |
278
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
52524-30
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:14570876-Animals,
pubmed-meshheading:14570876-Cell Line,
pubmed-meshheading:14570876-Coat Protein Complex I,
pubmed-meshheading:14570876-Dose-Response Relationship, Drug,
pubmed-meshheading:14570876-Endoplasmic Reticulum,
pubmed-meshheading:14570876-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:14570876-Glutathione Transferase,
pubmed-meshheading:14570876-Glyceraldehyde-3-Phosphate Dehydrogenase...,
pubmed-meshheading:14570876-Golgi Apparatus,
pubmed-meshheading:14570876-HeLa Cells,
pubmed-meshheading:14570876-Humans,
pubmed-meshheading:14570876-Isoenzymes,
pubmed-meshheading:14570876-Kidney,
pubmed-meshheading:14570876-Microsomes,
pubmed-meshheading:14570876-Mutation,
pubmed-meshheading:14570876-Phosphorylation,
pubmed-meshheading:14570876-Precipitin Tests,
pubmed-meshheading:14570876-Protein Binding,
pubmed-meshheading:14570876-Protein Kinase C,
pubmed-meshheading:14570876-Protein Structure, Tertiary,
pubmed-meshheading:14570876-Protein Transport,
pubmed-meshheading:14570876-Rats,
pubmed-meshheading:14570876-Recombinant Proteins,
pubmed-meshheading:14570876-Transfection,
pubmed-meshheading:14570876-Two-Hybrid System Techniques,
pubmed-meshheading:14570876-rab2 GTP-Binding Protein
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Rab2 interacts directly with atypical protein kinase C (aPKC) iota/lambda and inhibits aPKCiota/lambda-dependent glyceraldehyde-3-phosphate dehydrogenase phosphorylation.
|
| pubmed:affiliation |
Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA. etisdale@med.wayne.edu
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|