Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was performed to compare the effect of parathyroid hormone-related peptide (PTHrP) on bone resorption with that of parathyroid hormone (PTH) and clarify the participation of PTHrP-responsive dual signal transduction systems involving cAMP-dependent protein kinase (PKA) and calcium/protein kinase C (Ca/PKC) in the stimulation of bone resorption by PTHrP. Bone resorbing activity was estimated as the number of pits formed on the dentine slice and total area of pits per slice in bone cells derived from 2 week-old mice. Human (h)PTHrP-(1-34) (10(7) M) stimulated bone resorption as potent as hPTH-(1-34) (10(7) M) did. The stimulation of bone resorption by hPTHrP-(1-34) and hPTH-(1-34) was equally blocked by either simultaneous treatment with 10(-8) M Elcatonin (eel calcitonin derivative; from Asahi Chemical Industry, Tokyo, Japan) [corrected] or pretreatment with 10(-7) M [Nle8,18Tyr34]hPTH-(3-34)amide. Rp-cAMPs, an antagonist in the activation of PKA, equally attenuated bone resorption stimulated by PTHrP as well as by PTH. A23187 (10(-7) M) caused a significant stimulation of bone resorption. These findings indicate the direct involvement of PKA activation and a contributory role of an increase in cytosolic calcium in the stimulation of bone resorption by PTHrP and suggest that PTHrP stimulates bone resorption presumably through the same mechanism as PTH does.
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PMID:Role of dual signal transduction systems in the stimulation of bone resorption by parathyroid hormone-related peptide. The direct involvement of cAMP-dependent protein kinase. 822 86

Calcitonin is known to inhibit osteoclastic bone resorption through its receptor, which is abundantly expressed on the plasma membrane of osteoclasts. Recently, it was reported that calcitonin receptors were coupled to both cAMP-dependent protein kinase (PKA) and protein kinase C (PKC). To examine how the PKA and PKC pathways are involved in the effects of calcitonin, we focused on changes in the cytoskeleton of murine osteoclast-like multinucleated cells (OCLs) formed in vitro. When OCLs were cultured on dentine slices, they formed resorption pits and ringed structures of F-actin dots (actin rings). Elcatonin, a synthetic analogue of eel calcitonin, disrupted actin rings and inhibited pit formation in a dose-dependent manner. Forskolin and dibutyryl cAMP, both of which have the ability to activate PKA, mimicked the effects of elcatonin. Phorbol myristate acetate and phorbol 12,13-dibutyrate, both of which have the ability to activate PKC, also inhibited pit-forming activity, but little affected actin rings of OCLs. The inhibitory effects of elcatonin on the pit formation and actin ring formation were partially restored by the treatment with Rp-cAMPs, a cAMP antagonist. Elcatonin induced a rapid increase in PKA activity within a few minutes, and its activation by elcatonin occurred in a dose-dependent manner. The time- and dose-dependent profiles of elcatonin for the activation of PKA were similar to those for the disruption of actin rings. Moreover, microinjection of activated PKA into OCLs disrupted actin rings within 10 min on culture dishes. Actin rings were little affected by the microinjection of the PKA preincubated with a cAMP-dependent protein kinase inhibitor (IP-20) into OCLs. These results suggest that PKA activation, rather than PKC activation, is involved in mediating the effects of calcitonin, through the disruption of actin organization.
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PMID:Calcitonin-induced changes in the cytoskeleton are mediated by a signal pathway associated with protein kinase A in osteoclasts. 889 34