C-mip interacts with the p85 subunit of PI3 kinase and exerts a dual effect on ERK signaling via the recruitment of Dip1 and DAP kinase

Maud Kamal; Andre Pawlak; Fatima BenMohamed; Asta Valanciuté; Karine Dahan; Marina Candelier; Philippe Lang; Georges Guellaën; Djillali Sahali

doi:10.1016/j.febslet.2009.12.015

C-mip interacts with the p85 subunit of PI3 kinase and exerts a dual effect on ERK signaling via the recruitment of Dip1 and DAP kinase

FEBS Lett. 2010 Feb 5;584(3):500-6. doi: 10.1016/j.febslet.2009.12.015. Epub 2009 Dec 16.

Authors

Maud Kamal¹, Andre Pawlak, Fatima BenMohamed, Asta Valanciuté, Karine Dahan, Marina Candelier, Philippe Lang, Georges Guellaën, Djillali Sahali

Affiliation

¹ INSERM, U 955, Equipe 21, Créteil F-94010, France.

PMID: 20018188
DOI: 10.1016/j.febslet.2009.12.015

Abstract

In naive T cells, Lck exerts a negative control on the ERK/MAPK pathway. We show that c-mip (c-maf inducing protein) interacts with the p85 subunit of PI3 kinase and inactivates Lck, which results in Erk1/2 and p38 MAPK activation. This effect is not enough to activate AP1 given the inability of ERK to migrate into the nucleus and to transactivate its target genes. We demonstrate that c-mip interacts with Dip1 and upregulates DAPK, which blocks the nuclear translocation of ERK1/2. This dual effect of c-mip is unique and might represent a potential mechanism to prevent the development of an immune response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins / metabolism*
Blotting, Western
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cells, Cultured
Death-Associated Protein Kinases
Humans
Immunoprecipitation
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Phosphatidylinositol 3-Kinases / chemistry
Phosphatidylinositol 3-Kinases / metabolism*
Protein Binding / genetics
Protein Binding / physiology
Protein Subunits / genetics
Protein Subunits / physiology
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Transcription Factors / metabolism*
Two-Hybrid System Techniques

Substances

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
CCNDBP1 protein, human
CMIP protein, human
Carrier Proteins
Protein Subunits
Transcription Factors
Phosphatidylinositol 3-Kinases
Death-Associated Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3