Tyrosine kinase-associated receptors

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

Cytokine Receptors (Tyrosine Kinase-Associated Receptors) 109... 

Tyrosine kinase-associated receptors signal by recruiting activated cytosolic enzymes to the cell membrane. The resulting activation is similar to RTK signaling, but the kinase activity is not related directly to the receptor molecule. Classic examples of this type of receptor are cytokine receptors that modulate gene expression in immune cells as well as many... 

Tyrosine kinase-associated receptors called Jak-STAT receptors are often used by cytokines to regulate the proliferation of certain cells involved in the immune response (see Fig. 11.9B). The receptor itself has no intrinsic kinase activity but binds (associates with) the tyrosine kinase Jak (janus kinase). Their signal transducer proteins, called STATs (signal transducer and activator of transcription), are themselves gene-specific transcription factors. Thus, Jak-STAT receptors have a more direct route for propagation of the signal to the nucleus than tyrosine kinase receptors. 

Tyrosine Kinase Inhibitors/Receptor Associated Tyrosine Kinase Inhibitors (RTK-I)... 

The insulin receptor is composed of two heterodimers each heterodimer is composed of an a unit and a P unit. The a unit is extracellular and contains the insulin recognition and binding sites the p unit spans the cellular membrane and contains a tyrosine kinase. Although insulin can bind to a single ap dimer, it binds with higher affinity to the aPaP tetrameric complex. When insulin binds to an a unit, the tyrosine kinase associated with the corresponding p unit is stimulated. Following this, intracellular proteins such as IRS-1 and IRS-2 (IRS=insulin receptor substrate) are phosphorylated by the P subunit tyrosine kinase, and they in turn activate a network of phosphorylations within the receptor cell. 

Intracellular signal transduction employs central switching stations that receive, modulate and transmit signals further. The Ras proteins (also known as p2T proteins) make up a switching station of particular importance for growth and differentiation processes. The Ras proteins process signals received by receptor tyrosine kinases, by receptors with associated tyrosine kinase activity and by G-protein-coupled receptors, and transmit these into the cell interior (Fig. 9.1). 

CD3/cCD3 processes protein complex tyrosine kinase associated with T cell receptor (TCR) detected on cell surface or intracytoplasm (c)... 

Growth factor receptors (These receptors fall into two main groups receptor tyrosine kinases and receptors that associate with cytoplasmic tyrosine Insulin1 Insulin Lower blood glucose promote glucose storage as glycogen in liver and skeletal muscle and as fat in fat cells... 

Receptors associated with a tyrosine kinase Insulin receptor Insulin (agonist)... 

Erlotinib is an epidermal growth factor receptor inhibitor that inhibits intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor. It is indicated in the treatment of locally advanced or metastatic non-small-cell lung cancer after failure of at least 1 prior chemotherapy regimen. Erlotinib (Tarceva) is a human HER 1/EGER tyrosine kinase inhibitor with the following chemical formula A-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine. It is indicated in treatment of patients with locally advanced or metastatic non-small-cell lung cancer. 

Zhou, R. Copeland, T.D. Kromer, L.F. Schulz, N.T. Isolation and characterization of Bsk, a growth factor receptor-like tyrosine kinase associated with the limbic system. J. Neurosci. Res., 37, 129-143 (1994)... 

For proteins such as tyrosine-kinase receptors, dimerization (the association of two receptors to form a new species... 

Fyn is a nonreceptor tyrosine kinase related to Src that is frequently found in cell junctions. Die protein is N-myristoylated and palmitoylated and thereby becomes associated with caveolae-like membrane microdomains. Fyn can interact with a variety of other signaling molecules and control a diversity of biological processes such as T cell receptor signaling, regulation of brain function, and adhesion mediated signaling. 

Besides the cytokine receptors that lack intrinsic kinase activity but have associated JAK kinases, STAT proteins can be activated by a variety of G-protein coupled receptors and growth factor receptors with intrinsic tyrosine kinase activity (for example EGF, PDGF, CSF-1, and angiotensin receptor). Increasing evidence suggests a critical role for STAT family members in oncogenesis and aberrant cell proliferation. Constitutively activated STATs have been found in many transformed cell lines and a wide variety of human tumor entities. Numerous non-receptor tyrosine kinases and viral oncoproteins, such as v-Src, v-Abl, v-Sis, and v-Eyk, have been identified to induce DNA-binding activity of STAT proteins. 

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