Target type: biologicalprocess
Any process that stops, prevents, or reduces the frequency, rate, or extent of integrin activation. [GOC:add]
Negative regulation of integrin activation is a critical process that fine-tunes cell adhesion, migration, and signaling. Integrins, transmembrane receptors that connect the extracellular matrix to the cytoskeleton, are activated through a conformational change that exposes their ligand binding site. This activation is tightly controlled to prevent inappropriate adhesion and signaling. Several mechanisms are employed to negatively regulate integrin activation, including:
1. **Intracellular signaling pathways:**
* **Phosphorylation:** Specific kinases, such as focal adhesion kinase (FAK), Src family kinases, and protein kinase C (PKC), can phosphorylate integrin cytoplasmic tails or associated proteins, promoting integrin inactivation and preventing ligand binding.
* **GTPase activity:** Rho GTPases, particularly RhoA, are involved in regulating integrin activation. RhoA activation can lead to integrin clustering and activation, while RhoA inhibition can result in integrin inactivation.
* **Calcium signaling:** Increased intracellular calcium levels can trigger pathways that negatively regulate integrin activation, promoting detachment from the extracellular matrix.
2. **Cytoskeletal interactions:**
* **Actin dynamics:** Proper actin polymerization is essential for integrin activation. Disruption of actin filaments, such as through the action of cofilin or gelsolin, can lead to integrin inactivation.
* **Myosin activity:** Myosin motors contribute to integrin clustering and activation. Inhibition of myosin activity can negatively regulate integrin activation.
3. **Extracellular factors:**
* **Ligand binding:** The presence of certain extracellular ligands can promote integrin inactivation, for example, by triggering conformational changes that mask the ligand binding site.
* **Extracellular matrix components:** The composition and organization of the extracellular matrix can influence integrin activation. For example, the presence of certain ECM proteins or specific matrix stiffness can promote or inhibit integrin activation.
4. **Membrane trafficking:**
* **Endocytosis:** Integrins can be internalized through endocytosis, removing them from the cell surface and preventing further activation.
* **Recycling:** Internalized integrins can be recycled back to the cell surface, but this process is often regulated to control integrin activity.
These various mechanisms work in concert to ensure that integrin activation is carefully regulated, preventing excessive adhesion, promoting cell migration, and allowing cells to respond appropriately to their environment.'
"
Protein | Definition | Taxonomy |
---|---|---|
Prostaglandin E2 receptor EP4 subtype | [no definition available] | Canis lupus familiaris (dog) |
Prostaglandin E2 receptor EP4 subtype | A prostaglandin E2 receptor EP4 subtype that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35408] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
metergoline | metergoline : An ergoline alkaloid that is the N-benzyloxycarbonyl derivative of lysergamine. A 5-HT2 antagonist. Also 5-HT1 antagonist and 5-HT1D ligand. Has moderate affinity for 5-HT6 and high affinity for 5-HT7. Metergoline: A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy. | carbamate ester; ergoline alkaloid | dopamine agonist; geroprotector; serotonergic antagonist |
ah 6809 | 6-isopropoxy-9-oxoxanthene-2-carboxylic acid: structure given in UD | xanthones | |
dinoprostone | prostaglandin E2 : Prostaglandin F2alpha in which the hydroxy group at position 9 has been oxidised to the corresponding ketone. Prostaglandin E2 is the most common and most biologically potent of mammalian prostaglandins. | prostaglandins E | human metabolite; mouse metabolite; oxytocic |
dinoprost | Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions. prostaglandin F2alpha : A prostaglandins Falpha that is prosta-5,13-dien-1-oic acid substituted by hydroxy groups at positions 9, 11 and 15. It is a naturally occurring prostaglandin used to induce labor. | monocarboxylic acid; prostaglandins Falpha | human metabolite; mouse metabolite |
butaprost | |||
cloprostenol | Cloprostenol: A synthetic prostaglandin F2alpha analog. The compound has luteolytic effects and is used for the synchronization of estrus in cattle. | prostanoid | |
tg4-155 | TG4-155: an EP2 receptor antagonist; structure in first source | ||
mk-0524 | MK-0524: a potent orally active human prostaglandin D(2) receptor 1 antagonist; structure in first source | indolyl carboxylic acid | |
cp533536 | CP533536: an EP2 receptor-selective prostaglandin E2 agonist that induces bone healing; structure in first source | monocarboxylic acid | |
amg 009 | AMG 009: an anti-inflammatory agent; structure in first source | ||
dg 041 | |||
cj-042794 | aromatic ether | ||
gw9508 | GW9508: structure in first source | aromatic amine | |
cj-023,423 | grapiprant: a potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties; cyclooxygenase inhibitors | ||
l-798106 | L-798106 : An N-sulfonylcarboxamide resulting from the formal condensation of the carboxy group of o-naphthalen-2-ylcinnamic acid with the sulfonamide group of 5-bromo-2-methoxybenzenesulfonamide. It is a selective antagonist for the prostanoid receptor EP3, a prostaglandin receptor for prostaglandin E2 (PGE2). | aromatic ether; bromobenzenes; N-sulfonylcarboxamide | prostaglandin receptor antagonist |
cp 544326 | CP 544326: structure in first source | ||
fevipiprant | fevipiprant: a CRTh2 antagonist; structure in first source | ||
fr181157 | |||
pf-04418948 | 1-(4-fluorobenzoyl)-3-(((6-methoxy-2-naphthyl)oxy)methyl)azetidine-3-carboxylic acid: structure in first source | ||
cay 10580 | 2-(3-hydroxyoctyl)-5-oxo-1-pyrrolidineheptanoic acid : A pyrrolidin-2-one substituted by 6-carboxyhexyl and 3-hydroxyoctyl groups at positions 1 and 2, respectively. It is a potent prostaglandin EP4 receptor agonist (Ki=35 nM). CAY 10580: a E-prostanoid EP4 receptor agonist | hydroxy monocarboxylic acid; pyrrolidin-2-ones; secondary alcohol | prostaglandin receptor agonist |
tg6-10-1 | TG6-10-1: brain-permeant prostaglandin E receptor 2 antagonist; structure in first source |