PI3 kinase function is vital for the function but not formation of LAT-mediated signaling complexes

Noemi Cruz-Orcutt; Jon C D Houtman

doi:10.1016/j.molimm.2009.04.006

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PI3 kinase function is vital for the function but not formation of LAT-mediated signaling complexes

Journal article

Peer reviewed

PI3 kinase function is vital for the function but not formation of LAT-mediated signaling complexes

Noemi Cruz-Orcutt and Jon C D Houtman

Molecular immunology, Vol.46(11-12), pp.2274-2283

07/2009

DOI: 10.1016/j.molimm.2009.04.006

PMID: 19427038

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Abstract

The induction of the T cell receptor (TCR) is necessary for the activation and function of human T cells. TCR activation results in the tyrosine phosphorylation of LAT, leading to the direct interaction with several proteins, including PLC-gamma 1, Grb2 and Gads. These direct ligands then mediate the indirect interaction of LAT with proteins, such as SLP-76, Vav1 and Itk. PLC-gamma 1, Vav1 and Itk contain pleckstrin homology (PH) domains that interact with the enzymatic product of phosphoinositide-3-kinase (PI3K), suggesting the function of PI3K may modulate LAT-mediated complexes. Therefore, we characterized the poorly understood role of PI3K activity in the formation and function of multiprotein signaling complexes that form at LAT. Inhibition of PI3K catalytic function had little effect on the phosphorylation of LAT, SLP-76, Vav1 or PLC-gamma 1 or on the ability of PLC-gamma 1 to interact with LAT or SLP-76. However, PI3K activity appeared to be required for the induction of downstream signaling events. These data indicate that the formation of LAT-mediated complexes do not appear to depend on PI3K activity, whereas the optimal downstream function of these complexes requires the catalytic function of PI3K.

Cell Line

Phospholipase C gamma - metabolism

Phosphorylation

Signal Transduction

Humans

Phosphatidylinositol 3-Kinases - antagonists & inhibitors

Phosphoproteins - metabolism

Receptors, Antigen, T-Cell - physiology

Multiprotein Complexes - physiology

Adaptor Proteins, Signal Transducing - physiology

Phospholipase C gamma - immunology

T-Lymphocytes - metabolism

Membrane Proteins - physiology

Phosphatidylinositol 3-Kinases - physiology

Protein Binding

Adaptor Proteins, Signal Transducing - metabolism

Proto-Oncogene Proteins c-vav - metabolism

Details

Title: Subtitle: PI3 kinase function is vital for the function but not formation of LAT-mediated signaling complexes
Creators: Noemi Cruz-Orcutt - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Jon C D Houtman
Resource Type: Journal article
Publication Details: Molecular immunology, Vol.46(11-12), pp.2274-2283
DOI: 10.1016/j.molimm.2009.04.006
PMID: 19427038
ISSN: 0161-5890
eISSN: 1872-9142
Language: English
Date published: 07/2009
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984094563302771

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