Receptors with intrinsic enzymatic activity

Enzyme receptors are transmembrane receptors with intrinsic enzymatic activity. Examples are the receptor tyrosine kinases (RTKs), which autophosphorylate their own tyrosine residues, such as the growth factor receptors and the insulin receptor. And, finally, there are the intracellular DNA sinding receptors. They bind lipophilic ligands that pass through the membrane. They address genes directly. Examples are the steroid hormone receptors (see Chapter 11). (This figure was donated by Professor Martin Lohse, University of Wurzburg.)... 

Figure 7. Schematic of a receptor with intrinsic enzymatic activity. Ligand mediated activation results in phosphorylation of phospholipase C (y isoform) leading to hydrolysis of polyphosphoinositides (PIP2). Dia-cyl-glycerol (DAG) and inositol-triphosphate (IP3) are formed. 1P3 increases the release of stored calcium. Calcium together with DAG can activate PKC signalling pathway. Association of this type of receptor with adapter proteins results in activation of Ras/Raf/ERK signalling or in activation of PI3K/Akt signalling.

FIGURE 4.5 Gated ion channel receptors, receptors with intrinsic enzymatic activity and receptors associated with cytosohc tyrosine kinases. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

There are two distinct types of TNF receptors, TNF-R1 (CD120a or P55) and TNF-R2 (CD120b or P75). They are implicated in inflammatory processes and both belong to the TNF receptor superfamily. TNF receptors are transmembrane proteins with intracellular domains that lack intrinsic enzymatic activity, and consequently, they require cytoplasmic proteins that help initiate the receptor-induced signaling pathways. TNF-R1 possesses an intracellular death domain and TNF-R2 interacts with molecules of the TNF receptor-associated factor 2 family (TRAF). 

Receptors with Intrinsic or Associated Enzymatic Activity... 

As in signaling by cytokine receptors, phosphotyroslne residues in activated RTKs serve as docking sites for proteins involved in downstream signal transduction. Many phos-photyrosine residues in activated RTKs interact with adapter proteins, small proteins that contain SH2, PTB, or SH3 domains but have no intrinsic enzymatic or signaling activities (see Figure 14-6). These proteins couple activated RTKs to other components of signal-transduction pathways such as the one involving Ras activation. 

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