Solute Transport across Membranes:-The β-Adrenergic Receptor Is Desensitized by Phosphorylation

As noted earlier, signal-transducing systems undergo desensitization when the signal persists. Desensitization of the β -adrenergic receptor is mediated by a protein kinase that phosphorylates the receptor on the intra cellular domain that normally interacts with Gs (Fig. 12–17). When the receptor is occupied by epinephrine, β-adrenergic receptor kinase (β ARK) phosphory lates Ser residues near the carboxyl terminus of the receptor. Normally located in the cytosol, ARK is drawn to the plasma membrane by its association with th Gs subunits and is thus positioned to phosphorylate the receptor. The phosphorylation creates a binding site for the protein β-arrestin (βarr), also called arrestin 2, and binding of -arrestin effectively prevents interaction between the receptor and the G protein. The binding of β-arrestin also facilitates receptor sequestration, the removal of receptors from the plasma membrane by endocytosis into small intracellular vesicles. Receptors in the endocytic vesicles are dephosphorylated, then re turned to the plasma membrane, completing the circuit and resensitizing the system to epinephrine. β-Adrenergic receptor kinase is a member of a family of G protein coupled receptor kinases (GRKs), all of which phosphorylate serpentine receptors on their carboxyl-terminal cytosolic domains and play roles similar to that of ARK in desensitization and resensitization of their receptors. At least five different GRKs and four different arrestins are encoded in the human genome; each GRK is capable of desensitizing a subset of the serpentine receptors, and each arrestin can interact with many different types of phosphorylated receptors. While preventing the signal from a serpentine receptor from reaching its associated G protein, arrestins can also initiate a second signaling cascade, by acting as scaffold proteins that bring together several protein kinases that function in a cascade. For example, the β-arrestin associated with the serpentine receptor for angiotensin, a potent regulator of blood pressure, binds the three protein kinases Raf-1, MEK1, and ERK (Fig. 12–18), serving as a scaffold that facilitates any signaling process, such as insulin signaling (Fig. 12–6), that requires these three protein kinases to interact. This is one of many known examples of cross-talk between systems triggered by different ligands (angiotensin and insulin, in this case).

FIGURE 12–17 Desensitization of the -adrenergic receptor in the continued presence of epinephrine. This process is mediated by two proteins: β-adrenergic protein kinase (βARK) and β-arrestin (β arr; arrestin 2).

FIGURE 12–18 β-Arrestin uncouples the serpentine receptor from its G protein and brings together the three enzymes of the MAPK cascade. The effect is that one stimulus triggers two distinct response path ways: the path activated by the G protein and the MAPK cascade.

اخر الاخبار

اخبار العتبة العباسية المقدسة

ملتقى الكوثر الثالث يشهد عرض مشهد حواري بعنوان شريك العمر أم شريك الفكر؟

إقامة مسابقة (مرفأ النور) العلمية للمشاركات في فعاليات ملتقى الكوثر بنسخته الثالثة

ضمن ملتقى الكوثر الثالث.. ورشة تسلط الضوء على بناء الوعي القرآني لدى النساء

شعبة فاطمة بنت أسد (عليها السلام): ملتقى الكوثر منصةً لتحقيق وعي أسري مستند للقرآن الكريم

المزيد

الآخبار الصحية

نظام غذائي شائع قد يؤدي إلى ارتفاع الكوليسترول الضار

تحذيرات هامة من عواقب تناول "أيبوبروفين" مع أدوية شائعة

علامات مبكرة للإيبولا يمكن الخلط بينها وبين الإنفلونزا

خبراء: الفيروسات مثل هانتا وإيبولا أصبحت أكثر شيوعا وفتكاً

المزيد

الآخبار التكنلوجية

الليلة.. هلال القمر يلتقي كوكبي الزهرة والمشتري

إيلون ماسك يخسر دعواه القضائية أمام أوبن إيه.آي

مهمة فضائية "أوروبية صينية" لكشف أسرار الرياح الشمسية

انتهاء رحلة "السفينة الموبوءة".. وهذا مصير من بقي على متنها

المزيد

مواضيع ذات صلة

G Protein–Coupled Receptors and Second Messengers:-The -Adrenergic Receptor System Acts through the Second Messenger cAMP

Receptor Enzymes:- Receptor Guanylyl Cyclases Generate the Second Messenger cGMP

Receptor Enzymes: -The Insulin Receptor Is a Tyrosine-Specific Protein Kinase

Gated Ion Channels:- Neurons Have Receptor Channels That Respond to Different Neurotransmitters

Gated Ion Channels:- Voltage-Gated Ion Channels Produce Neuronal Action Potentials

Gated Ion Channels:- Ion Channels Underlie Electrical Signaling in Excitable Cells

Solute Transport across Membranes:- Defective Ion Channels Can Have Adverse Physiological Consequences

Solute Transport across Membranes:- The Acetylcholine Receptor Is a Ligand-Gated Ion Channel

Solute Transport across Membranes:- The Neuronal Na+ Channel Is a Voltage-Gated Ion Channel

Solute Transport across Membranes: -The Structure of a K+ Channel Reveals the Basis for Its Specificity

Solute Transport across Membranes:- Ion-Channel Function Is Measured Electrically

Solute Transport across Membranes:- Ion-Selective Channels Allow Rapid Movement of Ions across Membranes