タンパク質キナーゼAアンカリングタンパク質mAKAPは,2つの統合されたcAMPエフェクター経路を調整する
Kimberly L Dodge-Kafka1, Joseph Soughayer, Genevieve C Pare
1Howard Hughes Medical Institute, Oregon Health and Sciences University, Portland, Oregon 97239, USA.
Nature
|September 24, 2005
まとめ
筋肉細胞はmAKAPを使用してシグナル伝達タンパク質をアンカーし,局所化された循環性アデノシン3を作成します.
科学分野:
- 分子生物学は分子生物学である.
- セルラー・シグナリング
- バイオケミストリー バイオケミストリー
背景:
- 循環性アデノシン3',5'-モノフォスファート (cAMP) は,重要な細胞内伝達物質である.
- cAMPは,タンパク質キナーゼ (PKA),イオンチャネル,およびグアニンヌクレオチド交換因子 (Epacs) を調節する.
- リン酸エステラゼ (PDEs) はcAMPを代謝し,その局所的濃度を制御する.
研究 の 目的:
- 筋肉特異のA-キナーゼアンカリングタンパク質 (mAKAP) に固定されたcAMP反応性シグナル伝達複合体を特定し,特徴づけること.
- mAKAP複合体内のPKA,PDE4D3,Epac1の役割を明らかにする.
- この複合体の機能的な影響が心筋細胞のシグナル伝達に及ぼす影響を調査する.
主な方法:
- mAKAP複合体内のタンパク質相互作用を特定するための共免疫プレシピテーション.
- 信号伝達経路を変更するための薬理学および分子操作.
- 機能的な読み出しとして,心筋細胞高縮の評価.
主要な成果:
- mAKAP,PKA,PDE4D3,Epac1を含むシグナル伝達複合体が特定されました.
- 固定されたPKAはPDE4D3を活性化し,局所的なcAMPを減少させ,ERK5はPDE4D3.3を抑制する.
- PDE4D3はEpac1を勧誘し,CAMPに依存したERK5の衰弱を可能にし,これは心筋細胞過剰化を誘発する可能性があります.
結論:
- mAKAP複合体は,2つの結合したcAMP依存フィードバックループを調整する.
- AKAPタンパク質によるcAMPシグナル伝達の局所的な制御は複雑で,複雑なフィードバックメカニズムが含まれています.
- mAKAP複合体内のアンカーされたERK5シグナリングは,心筋細胞高縮に寄与する.
関連する概念動画
Microtubule Associated Proteins (MAPs)
4.8K
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.8K
Interactions Between Signaling Pathways
4.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.7K
MAPK Signaling Cascades
7.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K
PI3K/mTOR/AKT Signaling Pathway
5.1K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.1K
cAMP-dependent Protein Kinase Pathways
7.3K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.3K
Calmodulin-dependent Signaling
5.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.0K


