Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inositol 1,4,5-trisphosphate (IP(3)) is a second messenger that induces the release of Ca(2+) from the endoplasmic reticulum (ER). The IP(3) receptor (IP(3)R) was discovered as a developmentally regulated glyco-phosphoprotein, P400, that was missing in strains of mutant mice. IP(3)R can allosterically and dynamically change its form in a reversible manner. The crystal structures of the IP(3)-binding core and N-terminal suppressor sequence of IP(3)R have been identified. An IP(3) indicator (known as IP(3)R-based IP(3) sensor) was developed from the IP(3)-binding core. The IP(3)-binding core's affinity to IP(3) is very similar among the three isoforms of IP(3)R; instead, the N-terminal IP(3) binding suppressor region is responsible for isoform-specific IP(3)-binding affinity tuning. Various pathways for the trafficking of IP(3)R have been identified; for example, the ER forms a meshwork upon which IP(3)R moves by lateral diffusion, and vesicular ER subcompartments containing IP(3)R move rapidly along microtubles using a kinesin motor. Furthermore, IP(3)R mRNA within mRNA granules also moves along microtubules. IP(3)Rs are involved in exocrine secretion. ERp44 works as a redox sensor in the ER and regulates IP(3)R1 activity. IP(3) has been found to release Ca(2+), but it also releases IRBIT (IP(3)R-binding protein released with IP(3)). IRBIT is a pseudo-ligand for IP(3) that regulates the frequency and amplitude of Ca(2+) oscillations through IP(3)R. IRBIT binds to pancreas-type Na, bicarbonate co-transporter 1, which is important for acid-base balance. The presence of many kinds of binding partners, like homer, protein 4.1N, huntingtin-associated protein-1A, protein phosphatases (PPI and PP2A), RACK1, ankyrin, chromogranin, carbonic anhydrase-related protein, IRBIT, Na,K-ATPase, and ERp44, suggest that IP(3)Rs form a macro signal complex and function as a center for signaling cascades. The structure of IP(3)R1, as revealed by cryoelectron microscopy, fits closely with these molecules.
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PMID:IP3 receptor/Ca2+ channel: from discovery to new signaling concepts. 1769 45

Inositol 1,4,5-trisphosphate (IP3) is a second messenger that induces the release of calcium from the endoplasmic reticulum (ER). The IP3 receptor was discovered as a developmentally regulated glycophosphoprotein, P400, that is absent in strains of mutant mice. The crystal structures of the IP3-binding core and N-terminal suppressor sequence of the IP3 receptor have been identified. The IP3-binding core's affinity to IP3 is similar among the three isoforms of IP3 receptors; however, the N-terminal IP3-binding suppressor region is responsible for isoform-specific IP3-binding affinity tuning. Various pathways for the trafficking of IP3 receptors have been identified; for example, the ER forms a meshwork on which IP3 receptors move by lateral diffusion, and vesicular ER subcompartments containing IP3 receptors move rapidly along microtubules using a kinesin motor. Furthermore, IP3 receptor messenger RNA within messenger RNA granules also moves along microtubules. Recently, we discovered that IP3 receptors play a crucial role in exocrine secretion. ERp44 works as a redox sensor in the ER and regulates IP3 type 1 receptor activity. IP3 receptor also releases IP3 receptor-binding protein released with IP3 (IRBIT). IRBIT is a pseudoligand for IP3 that regulates the frequency and amplitude of calcium oscillations through the IP3 receptor. IRBIT binds to pancreas-type sodium bicarbonate cotransporter 1, which is important for acid-base balance. Type 2 and 3 double-deficient mice show a deficit in saliva and lacrimal and pancreatic juice secretion. Type 1 IP3 receptor influences brain-derived neurotrophic factor production.
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PMID:The role of Ca2+ signaling in cell function with special reference to exocrine secretion. 1881 72