Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular mechanisms controlling reabsorption of amino acids in the renal proximal tubule are unknown. Ca(2+)-dependent protein kinases modulate the activity of several ion channels and carriers in the kidney. The role of these enzymes in regulating tubular amino acid transport has not been established. We investigated the effect of Ca(2+)- and phospholipid-dependent protein kinase C (PKC) and Ca2+/calmodulin-dependent protein kinase II (CaMK II) on Na(+)- and Cl(-)-dependent proline transport across the rat renal brush-border membrane (BBM). Bioassays utilizing selective peptide substrates for Ca(2+)-dependent protein kinases demonstrated the presence of PKC and CaMK II in the BBM. Renal brush-border membrane vesicles (BBMV) were phosphorylated using the "hyposmotic shock" technique. Endogenous (membrane-bound) CaMK II and PKC, as well as exogenous, highly purified PKC inhibited NaCl-linked proline uptake by phosphorylated, lysed/resealed BBMV compared with control vesicles. The inhibitory effect of Ca2+ on proline transport, without the presence of other kinase activators, was mediated by activation of endogenous CaMK II. The CaMK II- and PKC-induced inhibition of proline uptake was reversed by the specific kinase inhibitor peptides CaMK II-(281-302) and PKC-(19-31), respectively. These data suggest that Ca(2+)-dependent protein kinase-mediated phosphorylation inhibits NaCl-dependent proline transport across the tubular luminal membrane.
 ...
PMID:Ca(2+)-dependent protein kinases modulate proline transport across the renal brush-border membrane. 784 Feb 41

Changes in tubular reabsorption of amino acids and other solutes are characteristic of the immature renal tubule and of various hereditary nephropathies. The cellular mechanisms governing these aberrations in renal amino acid transport have not been established. Calcium (Ca2+)-dependent protein kinases are known to phosphorylate membrane-bound carrier proteins, thereby modulating transport of various solutes by the proximal tubule. The role of these enzymes in regulating renal tubular amino acid transport, particularly during kidney development, is unknown. We investigated: (1) the effect of Ca(2+)- and phospholipid-dependent protein kinase [protein kinase C (PKC)] and Ca2+/calmodulin-dependent protein kinase II (CaMKII) on sodium chloride (NaCl)-linked proline transport by renal brush border membrane vesicles (BBMV) from adult rats using the "hypoosmotic shock" technique (lysis of vesicles); (2) the activity, expression and subcellular distribution (cytosol, particulate, BBM) of Ca(2+)-dependent protein kinases in kidneys from 7-day-old and adult rats using MBP 4-14 and autocamtide II phosphorylation assays for PKC and CaMKII, respectively, endogenous protein phosphorylation (using gel electrophoresis and autoradiography) and Western immunoblot analysis to detect PKC and CaMKII. The studies showed: (1) endogenous (membrane-bound) CaMKII and PKC as well as exogenous, highly purified PKC inhibit proline uptake by phosphorylated, lyzed/resealed BBMV when compared with control vesicles; the voltage-clamped, nonelectrogenic component of proline transport was inhibited by PKC- but not CaMKII-mediated phosphorylation; (2) a Ca(2+)-dependent activity of both kinases was evident in all subcellular fractions tested in immature and adult kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The role of protein phosphorylation in renal amino acid transport. 825 36

Neuropeptide Y (NPY) has at least three receptors (Y1, Y2, and Y3) through which it influences different mechanisms in many cell types. Previous data suggest that the Y2 receptor may be divided into prejunctional and postjunctional subgroups. We have examined the intracellular signalling pathways of the postjunctional Y2 receptor in rat renal proximal tubules. The results indicate that NPY regulates Na+,K(+)-ATPase through several signalling pathways: (1) In proximal tubule (PT) cells NPY increased intracellular calcium. The response was blocked by removing extracellular calcium and was also blocked by using nifedipine. This suggests that calcium was increased by influx from the extracellular space through L-type calcium channels. (2) NPY increased Na+,K(+)-ATPase activity in PT segments and this effect was also blocked by nifedipine. CaMKII-Ala286[281-302] a blocker of Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibited the NPY-stimulated Na+,K(+)-ATPase activity. This implies that increased intracellular calcium activates CaMKII which subsequently increases Na+,K(+)-ATPase activity. CaMKII thus appear to act similar to what has been proposed for protein phosphatase 2B. (3) Calphostin C, an inhibitor of protein kinase C (PKC), did not inhibit NPY-stimulated Na+,K(+)-ATPase activity. PKC is, therefore, unlikely to be involved. (4) Y2 receptors are negatively coupled to the cAMP pathway. NPY attenuated forskolin-stimulated cAMP production in renal tubules and exogenous cAMP counteracted the NPY-stimulated Na+,K(+)-ATPase activity. This illustrated the importance of NPY for the regulation of renal sodium handling. We also propose that the renal tubule cell is a good model for studying the function and mechanisms of postjunctional Y2 receptors.
 ...
PMID:Neuropeptide Y regulates rat renal tubular Na,K-ATPase through several signalling pathways. 887 53

We examined the effect of glucocorticoids on brush border membrane transporters and, furthermore, the involvement of Ca2+ in its action in the primary cultured rabbit renal proximal tubule cells (PTCs). Dexamethasone (DEX, 10(-9) M) decreased Pi uptake by 17%; whereas DEX affected neither alpha-methyl-glucopyranoside (alpha-MG) uptake nor Na+ uptake. The DEX-induced inhibition of Pi uptake was due to a decrease of V(max). In contrast, other steroid hormones such as progesterone, testosterone, and 17beta-estradiol (10(-9) M) did not induce inhibition of Pi uptake. In order to examine the involvement of Ca2+ in DEX-induced inhibition of Pi uptake, PTCs were treated with A 23187 (10(-6) M, Ca2+ ionophore). A 23187 also inhibited Pi uptake, mimicking DEX action in Pi uptake. Treatments with W-7 (10(-4) M, calmodulin dependent kinase inhibitor), KN-62 (10(-6) M, Ca2+/calmodulin-dependent protein kinase II inhibitor), and BAPTA/AM (10(-6) M) or TMB-8 (10(-4) M) (intracellular Ca2+ mobilization blockers) blocked the DEX-induced inhibition of Pi uptake. However, nifedifine, methoxyverapamil (10(-6) M, L-type Ca2+ channel blockers), and EGTA (1 mM, extracellular Ca2+ chelator) did not block it. In conclusion, DEX inhibited Pi uptake via, in part, Ca2+/calmodulin pathway mediated by intracellular Ca2+ mobilization in the PTCs.
 ...
PMID:Regulatory mechanism of polarized membrane transport by glucocorticoid in renal proximal tubule cells: involvement of [Ca2+]i. 1059 76

Alteration of [Ca2+]i by hyperglycemia is implicated in the pathogenesis of diabetic nephropathy. However, the effect of high glucose on Ca2+ regulation in proximal tubule cells is not known. Thus, we examined the mechanisms by which high glucose regulates Ca2+ uptake in primary cultured rabbit renal proximal tubule cells. Glucose increased the Ca2+ uptake in a time- and dose-dependent manner. A stimulatory effect of high glucose on Ca2+ uptake is predominantly observed using 25 mM glucose (high glucose) after 1 h, while 25 mM glucose did not affect cell viability and lactate dehydrogenase release. However, 25 mM mannitol and L-glucose did not affect Ca2+ uptake as compared with controls. Nifedipine and methoxyverapamil (L-type Ca2+ channel blockers) blocked high-glucose-induced stimulation of Ca2+ uptake. High-glucose-induced stimulation of Ca2+ uptake was blocked by pertussis toxin, SQ-22536 (adenylate cyclase inhibitor), myristoylated amide 14-22 (protein kinase A inhibitor), neomycin and U-73122 (phospholipase C inhibitors), and staurosporine and bisindolylmaleimide I (protein kinase C inhibitors). In addition, KN-62 (a Ca2+/calmodulin-dependent protein kinase II inhibitor) and W-7 (a Ca2+/calmodulin antagonist) blocked high-glucose-induced stimulation of Ca2+ uptake. In conclusion, high glucose stimulates the Ca2+ uptake through L-type Ca2+ channels via G-protein-coupled adenylate cyclase/cAMP and phospholipase C/protein kinase C pathways.
 ...
PMID:High glucose stimulates Ca2+ uptake via cAMP and PLC/PKC pathways in primary cultured renal proximal tubule cells. 1117 1

Angiotensin II (ANG II) stimulates renal tubular reabsorption of NaCl by targeting Na(+)/H(+) exchanger NHE3. We have shown previously that inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) plays a critical role in stimulation of NHE3 in response to elevated intracellular Ca(2+) concentration ([Ca(2+)](i)). In this study, we investigated the role of IRBIT in mediating NHE3 activation by ANG II. IRBIT is abundantly expressed in the proximal tubules where NHE3 is located. ANG II at physiological concentrations stimulates NHE3 transport activity in a model proximal tubule cell line. ANG II-induced activation of NHE3 was abrogated by knockdown of IRBIT, whereas overexpression of IRBIT enhanced the effect of ANG II on NHE3. ANG II transiently increased binding of IRBIT to NHE3 at 5 min but became dissociated by 45 min. In comparison, it took at least 15 min of ANG II treatment for an increase in NHE3 activity and NHE3 surface expression. The stimulation of NHE3 by ANG II was dependent on changes in [Ca(2+)](i) and Ca(2+)/calmodulin-dependent protein kinases II. Inhibition of CaMKII completely blocked the ANG II-induced binding of IRBIT to NHE3 and the increase in NHE3 surface abundance. Several serine residues of IRBIT are thought to be important for IRBIT binding. Mutations of Ser-68, Ser-71, and Ser-74 of IRBIT decreased binding of IRBIT to NHE3 and its effect on NHE3 activity. In conclusion, our current findings demonstrate that IRBIT is critically involved in mediating activation of NHE3 by ANG II via a Ca(2+)/calmodulin-dependent protein kinases II-dependent pathway.
 ...
PMID:Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II. 2058 8