In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.

Ex Input:
T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCRalphabeta ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRalphabeta ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRalphabeta is transmitted to the CD3 subunits and to the intracellular signaling machinery.

Ex Output:
Full activation of the T cell receptor requires both clustering and conformational changes at CD3.

Ex Input:
US28 is one of four 7 transmembrane (7TM) chemokine receptors encoded by human cytomegalovirus and has been shown to both signal and endocytose in a ligand-independent, constitutively active manner. Here we show that the constitutive activity and constitutive endocytosis properties of US28 are separable entities in this viral chemokine receptor. We generated chimeric and mutant US28 proteins that were altered in either their constitutive endocytic (US28 Delta 300, US28 Delta 317, US28-NK1-ctail, and US28-ORF74-ctail) or signaling properties (US28R129A). By using this series of mutants, we show that the cytoplasmic tail domain of US28 per se regulates receptor endocytosis, independent of the signaling ability of the core domain of US28. The constitutive endocytic property of the US28 c-tail was transposable to other 7TM receptors, the herpes virus 8-encoded ORF74 and the tachykinin NK1 receptor (ORF74-US28-ctail and NK1-US28-ctail). Deletion of the US28 C terminus resulted in reduced constitutive endocytosis and consequently enhanced signaling capacity of all receptors tested as assessed by inositol phosphate turnover, NF-kappa B, and cAMP-responsive element-binding protein transcription assays. We further show that the constitutive endocytic property of US28 affects the action of its chemokine ligand fractalkine/CX3CL1 and show that in the absence of the US28 C terminus, fractalkine/CX3CL1 acts as an agonist on US28. This demonstrates for the first time that the endocytic properties of a 7TM receptor can camouflage the agonist properties of a ligand.

Ex Output:
The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis.

Ex Input:
The c-Jun N-terminal kinases (JNKs) are key regulators of inflammation and interfere with insulin action in cultured cells and whole animals. Obesity increases total JNK activity, and JNK1, but not JNK2, deficiency results in reduced adiposity and improved insulin sensitivity. Interestingly, a higher-than-normal level of JNK activation is observed in Jnk2(-/-) mice, particularly in the liver, indicating an interaction between the isoforms that might have masked the metabolic activity of JNK2 in isolated mutant mice. To address the role of the JNK2 isoform in metabolic homeostasis, we intercrossed Jnk1(-/-) and Jnk2(-/-) mice and examined body weight and glucose metabolism in the resulting mutant allele combinations. Among all of the viable genotypes examined, we observed only reduced body weight and increased insulin sensitivity in Jnk1(-/-) and Jnk1(+/-)Jnk2(-/-) mice. These two groups of mice also exhibited reduced total JNK activity and cytokine expression in liver tissue compared with all other genotypes examined. These data indicate that the JNK2 isoform is also involved in metabolic regulation, but its function is not obvious when JNK1 is fully expressed because of regulatory crosstalk between the two isoforms.

Ex Output:
Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance.