Datasheet

生物学的記述

Specificity	CAMKIV Antibody (Rabbit mAb) [P4P15] detects endogenous levels of total CAMKIV protein.
Background	Calcium/calmodulin-dependent protein kinase IV (CaMKIV/CAMK4) is a serine/threonine protein kinase within the Ca2+/calmodulin-dependent kinase family that operates as a nuclear effector of Ca2+ signaling and regulates transcriptional programs in lymphocytes, neurons and male germ cells through phosphorylation of multiple transcription activators. The kinase contains a catalytic domain, an autoinhibitory Ca2+/calmodulin-binding segment and regulatory regions that allow activation by Ca2+/calmodulin and phosphorylation at a threonine residue in the activation loop by upstream CaMKK, followed by intramolecular autophosphorylation that confers autonomous activity even after Ca2+/calmodulin dissociation. Activated CaMKIV is enriched in the nucleus and its best-characterized substrates include CREB, serum response factor and CREB-binding protein; phosphorylation of CREB on Ser133 by CaMKIV enhances CREB transcriptional activity and provides a mechanistic link between transient Ca2+ elevations and more sustained changes in gene expression required for long-term neuronal plasticity and memory consolidation. CaMKIV associates with protein phosphatase 2A via its Ca2+/calmodulin-binding autoinhibitory domain, and PP2A binding is mutually exclusive with Ca2+/calmodulin binding; PP2A dephosphorylates Thr200 in CaMKIV and terminates its autonomous activity, establishing a sequential activation–inactivation cycle in which Ca2+/calmodulin and CaMKK drive T200 phosphorylation and transcriptional stimulation, followed by PP2A-mediated dephosphorylation that limits signal duration. Importin α transports CaMKIV to the nucleus in a manner that does not depend on kinase activity or Ca2+/calmodulin binding, and nuclear localization supports efficient phosphorylation of transcriptional regulators in CREB-mediated signaling pathways, emphasizing that spatial control of CaMKIV is a key element of its function. In Wnt/β‑catenin signaling, the CaMKIV promoter contains TCF/LEF motifs, and canonical Wnt stimulation via Wnt‑3a or lithium increases CaMKIV mRNA and protein expression and promoter activity in hippocampal neurons, with β‑catenin binding to the CaMKIV promoter; Wnt pathway activation in a double transgenic Alzheimer’s disease mouse model restores CaMKIV expression and improves spatial memory, indicating that CaMKIV is a Wnt target gene linked to neuroprotective effects against amyloid pathology. CaMKIV participates in distinct prosurvival pathways in neurons, where dominant-inhibitory CaMKIV alters survival signaling differently from CaMKII inhibition, reinforcing its specific role in coupling Ca2+ signals to long-term transcriptional responses rather than to immediate cytosolic events. Beyond the nervous system, CaMKIV contributes to immune regulation by controlling transcription in lymphocytes and regulating T-cell maturation, dendritic cell survival and cytokine-related inflammatory responses, and it also influences bone growth, sperm motility, microtubule dynamics, cell-cycle progression and apoptosis, placing the kinase at the center of Ca2+-responsive transcriptional control across multiple tissues. Dysregulated CAMKIV activity or expression is associated with cerebral hypoxia, azoospermia, endometrial and ovarian cancers and systemic lupus, supporting interest in CaMKIV as a therapeutic target where its modular domain structure, Ca2+/calmodulin dependence, CaMKK–PP2A regulatory axis and nuclear localization can be exploited to modulate gene expression programs in disease settings.

Specificity

CAMKIV Antibody (Rabbit mAb) [P4P15] detects endogenous levels of total CAMKIV protein.

Background

Calcium/calmodulin-dependent protein kinase IV (CaMKIV/CAMK4) is a serine/threonine protein kinase within the Ca2+/calmodulin-dependent kinase family that operates as a nuclear effector of Ca2+ signaling and regulates transcriptional programs in lymphocytes, neurons and male germ cells through phosphorylation of multiple transcription activators. The kinase contains a catalytic domain, an autoinhibitory Ca2+/calmodulin-binding segment and regulatory regions that allow activation by Ca2+/calmodulin and phosphorylation at a threonine residue in the activation loop by upstream CaMKK, followed by intramolecular autophosphorylation that confers autonomous activity even after Ca2+/calmodulin dissociation. Activated CaMKIV is enriched in the nucleus and its best-characterized substrates include CREB, serum response factor and CREB-binding protein; phosphorylation of CREB on Ser133 by CaMKIV enhances CREB transcriptional activity and provides a mechanistic link between transient Ca2+ elevations and more sustained changes in gene expression required for long-term neuronal plasticity and memory consolidation. CaMKIV associates with protein phosphatase 2A via its Ca2+/calmodulin-binding autoinhibitory domain, and PP2A binding is mutually exclusive with Ca2+/calmodulin binding; PP2A dephosphorylates Thr200 in CaMKIV and terminates its autonomous activity, establishing a sequential activation–inactivation cycle in which Ca2+/calmodulin and CaMKK drive T200 phosphorylation and transcriptional stimulation, followed by PP2A-mediated dephosphorylation that limits signal duration. Importin α transports CaMKIV to the nucleus in a manner that does not depend on kinase activity or Ca2+/calmodulin binding, and nuclear localization supports efficient phosphorylation of transcriptional regulators in CREB-mediated signaling pathways, emphasizing that spatial control of CaMKIV is a key element of its function. In Wnt/β‑catenin signaling, the CaMKIV promoter contains TCF/LEF motifs, and canonical Wnt stimulation via Wnt‑3a or lithium increases CaMKIV mRNA and protein expression and promoter activity in hippocampal neurons, with β‑catenin binding to the CaMKIV promoter; Wnt pathway activation in a double transgenic Alzheimer’s disease mouse model restores CaMKIV expression and improves spatial memory, indicating that CaMKIV is a Wnt target gene linked to neuroprotective effects against amyloid pathology. CaMKIV participates in distinct prosurvival pathways in neurons, where dominant-inhibitory CaMKIV alters survival signaling differently from CaMKII inhibition, reinforcing its specific role in coupling Ca2+ signals to long-term transcriptional responses rather than to immediate cytosolic events. Beyond the nervous system, CaMKIV contributes to immune regulation by controlling transcription in lymphocytes and regulating T-cell maturation, dendritic cell survival and cytokine-related inflammatory responses, and it also influences bone growth, sperm motility, microtubule dynamics, cell-cycle progression and apoptosis, placing the kinase at the center of Ca2+-responsive transcriptional control across multiple tissues. Dysregulated CAMKIV activity or expression is associated with cerebral hypoxia, azoospermia, endometrial and ovarian cancers and systemic lupus, supporting interest in CaMKIV as a therapeutic target where its modular domain structure, Ca2+/calmodulin dependence, CaMKK–PP2A regulatory axis and nuclear localization can be exploited to modulate gene expression programs in disease settings.

使用情報

Application

WB, IF

Dilution

WB	IF
1:100000	1:50

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

52 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

プロトコール

References

https://pubmed.ncbi.nlm.nih.gov/26773169/
https://pubmed.ncbi.nlm.nih.gov/15143065/

CAMKIV Antibody (Rabbit mAb) [P4P15]

生物学的記述

使用情報

References

Application Data