Role of PKD in cell growth and apoptosis

Información del proyecto

Identificador del acuerdo de subvención: INTAS-2001-02118

Proyecto cerrado

Fecha de inicio 1 Junio 2002

Fecha de finalización 31 Mayo 2005

Financiado con arreglo a

• International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993-

Coste total

Sin datos

Aportación de la UE

€ 60 000,00

Coordinado por

Katholieke Universiteit Leuven
Belgium

Objetivo

Recent research has identified PKD/PKCµ as a protein kinase that plays important roles in cell surface receptor and growth factor signalling as well as in stress-induced signalling by genotoxic chemotherapeutics, radiation, and oxygen radicals. Moreover, PKD/PKCµ acts as an important DAG-stimulated negative feedback regulator of plasma membrane enzymes and receptors and mediates the cross talk between different signalling systems. The recent discovery of additional kinases which belong to the PKD family and the plethora of proteins that interact with PKD/PKCµ points to a multifaceted regulation and a multifunctional role for these enzymes, with functions in processes as diverse as cell proliferation, tumor cell invasion, and regulation of Golgi vesicle fission.

The main objectives of the project are:
A. To elucidate the molecular architecture of PKD;
B.To examine how PKD activation affects p53-dependent and -independent pathways responsible for regulation of apoptosis and cell cycle checkpoints and;
C. To investigate the role of PKD in carcinogenesis.

Specific tasks of this project will be:
T1. Molecular dissection of PKD structure and function;
T2.To develop molecular tools for the detection of protein kinase D;
T3. To investigate the role of PKD in p53-upstream and p53-downstream signalling;
T4.To investigate the role of PKD in B cell signalling;
T5.To assess the role of PKD in carcinogenesis.

A wide range of biochemical, immunological, cell death, computational and molecular biology methods will be applied Among them electron and confocal microscopy, immunocytochemistry, Fluorescence-activated cell sorting, Western blot analisis, site directed mutagenesis, phosphorylation assays, phosphopeptide sequencing techniques, yeast two-hybrid system, cell cycle analysis, antisense technology. Potential results will be expected: the molecular structure of PKD of its activation will be investigated; the role of PKD in different signal cascades associated with cell growth and apoptosis, will be determined; the potential links between the activities of PKD and p53, the most frequently mutated gene in human cancer will be clarified, the role of PKD in B- and T-cell regulation will be studied; the molecular insights in PKD function will be used to design therapeutics that inhibit the action of PKD.

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Programa(s)

• IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993-

Tema(s)

• 4 - Life Sciences
• OPEN - OPEN Call

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

Datos no disponibles

Coordinador

Katholieke Universiteit Leuven

• Aportación de la UE: Sin datos
• Dirección: Gasthuisberg, Herestraat 49 ; 3000 Leuven ; Bélgica
• Coste total: Sin datos

Participantes (3)

Medical University of Ulm

Alemania

• Aportación de la UE: Sin datos
• Dirección: Robert Koch Str. 8 ; 89081 Ulm
• Coste total: Sin datos

R.E.Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of the Ukraine

Ucrania

• Aportación de la UE: Sin datos
• Dirección: Vasilkovskaya Street 45 ; 03022 Kiev
• Coste total: Sin datos

Russian Academy of Medical Sciences

Rusia

• Aportación de la UE: Sin datos
• Dirección: Laboratory of Cytogenetics and Molecular Genetics ; 115478 Moscow
• Coste total: Sin datos