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Table of contents
INTRODUCTION
Tyrosine kinase signaling and the FAK family
1. The origin of TKs and FAK family
2. FAK family
Identification of FAK family kinases
Structure of FAK family kinases
2.2.1. FERM domain
2.2.2. Linker 1
2.2.3. Kinase domain
2.2.4. Linker 2
2.2.5. FAT domain
Expression of FAK and Pyk2
Cellular localization of FAK family kinases
Isoforms of FAK family kinases
2.5.1. FAK isoforms
2.5.2. Pyk2 isoforms
Biological functions of FAK
2.6.1. Cellular functions of FAK
2.6.2. Physiological functions of FAK
Pyk2: a nRTK of FAK family
1. Regulation of Pyk2 activity in non-neuronal cells
Activation and phosphorylation of Pyk2
1.1.1. Canonical activation of Pyk2
1.1.2. Regulation of Pyk2 activation by Ca2+-activated kinases
1.1.2.1. PKC
1.1.2.2. CaMKII
Dephosphorylation of Pyk2
1.2.1. Tyrosine phosphatases
1.2.1.1. SHP-1
1.2.1.2. SHP-2
1.2.1.3. PTP-PEST
1.2.1.4. STEP
1.2.2. Ser/Thr phosphatases
SUMOylation of Pyk2
S-nitrosylation of Pyk2
2. Pyk2 functions in non-neuronal cells
Pyk2 cellular functions
2.1.1. Cell adhesion
2.1.2. Cell migration
2.1.3. Cell division
2.1.4. Cell survival
2.1.5. Cell differentiation
Physiological role of Pyk2
2.2.1. Bone physiology
2.2.2. Vascular system integrity
2.2.3. Immune system function
2.2.4. Kidney function
2.2.5. Sperm capacitation
2.2.6. Generation of Pyk2 knockout mice
3. Pathological role of Pyk2
Pyk2 and inflammatory diseases
Pyk2 and cancers
Pharmacological inhibitors of Pyk2
Roles of Pyk2 in the CNS
1. Specific regulation of Pyk2 in the CNS
Activation of Pyk2 in neurons
Regulation of Pyk2 localization
2. Pyk2 biological functions in the CNS
Ionic channels regulation
2.1.1. Kv1.2
2.1.2. BK channels
2.1.3. NMDA receptor (NMDAR)
Development
Synaptic plasticity
Neuronal survival
Pyk2 in glial cells
3. Pyk2 in CNS diseases
Alzheimer·s disease
Parkinson·s disease
Huntington·s disease
Neuroinflammation
Glioma and neuroblastoma
Cerebral ischemia
Psychiatric disorders
RESULTS
Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington’s disease model
1. Context and objectives
2. Contribution to the work
3. Article
4. Summary of the findings and conclusions
Pyk2 in the amygdala modulates chronic stress sequelae via PSD-95-related microstructural changes
1. Context and objectives
2. Contribution to the work
3. Article
4. Summary of the findings and conclusions
PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer’s disease
1. Context and objectives
2. Contribution to the work
3. Article
4. Summary of the findings and conclusions
Conditional BDNF Delivery from Astrocytes Rescues Memory Deficits, Spine Density, and Synaptic Properties in the 5xFAD Mouse Model of Alzheimer Disease
1. Context and objectives
2. Contribution to the work
3. Article
4. Summary of the findings and conclusions
Pyk2 in nucleus accumbens D1 receptor-expressing neurons is selectively involved in the acute locomotor response to cocaine
1. Context and objectives
2. Contribution to the work
3. Article
4. Summary of the findings and conclusions
Supplementary data: spine density and morphology in the NAc of Pyk2-/- mice
1. Materials and methods
2. Results
DISCUSSION
Role of Pyk2 in memory
Kinase-dependent and independent functions of Pyk2
Antagonistic effect of Pyk2 on spine density and morphology
BDNF and Pyk2 merging functions
Pyk2 and AD: risk or rescue factor?
Contrasted function of Pyk2 in the striatum
BIBLIOGRAPHY
