甲状腺ホルモンおよび甲状腺ホルモンに関連するペプチドのGタンパク質結合受容体
H Jüppner1, A B Abou-Samra, M Freeman
1Endocrine Unit, Massachusetts General Hospital, Boston 02114.
まとめ
研究者は,新しい副甲状腺ホルモン-副甲状腺ホルモン関連ペプチド (PTH-PTHrP) 受容体をクローンし,両リガンドに対する同等の結合親和性と,新しいカルシウム調節ホルモン受容体ファミリーにおけるその役割を実証しました.
科学分野:
- 分子内分泌学分子内分泌学
- 受容体生物学 受容体生物学
- カルシウムホメオスタシス
背景:
- 副甲状腺ホルモン (PTH) と副甲状腺ホルモン関連ペプチド (PTHrP) は,カルシウムの重要な調節因子である.
- それらの受容体相互作用を理解することは,カルシウム代謝の研究にとって極めて重要です.
研究 の 目的:
- PTH-PTHrP受容体をコードする補完DNA (cDNA) をクローンして特徴づけること.
- 新型受容体の結合親和性とシグナル伝達能力を調査する.
主な方法:
- COS-7発現とオポッサムの腎臓細胞のcDNAライブラリを使用して,受容体cDNAのクローニング.
- PTHとPTHrPに対するリガンド結合親和性を評価する.
- PTHとPTHrPによるアデニラートサイクラゼ刺激の測定.
主要な成果:
- 7つのトランスメブランドメインを持つ585アミノ酸受容体をクローンに成功しました.
- 発現した受容体は,PTHとPTHrPの両方に等しい結合親和性を示した.
- 両方のリガンドは同等にアデニル酸サイクラース活性を刺激した.
結論:
- クローンされた受容体はPTHとPTHrPの両方に結合し,反応する.
- 構造的ホモロジーは,カルシウム調節ホルモン,カルシトニン受容体を含むGタンパク質に結合した受容体の新しい家族を示唆しています.
関連する概念動画
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...


