Phosphorylation of each of the distal three tyrosines of the CD28 cytoplasmic tail is required for CD28-induced T cell IL-2 secretion Journal Article

  

Authors:	Teng, J. M. C.; King, P. D.; Sadra, A.; Liu, X.; Han, A.; Selvakumar, A.; August, A.; Dupont, B.
Article Title:	Phosphorylation of each of the distal three tyrosines of the CD28 cytoplasmic tail is required for CD28-induced T cell IL-2 secretion
Abstract:	Signaling by the CD28 T cell costimulatory receptor is known to involve recruitment and activation of phosphatidylinositol 3-kinase (PI3-kinase) which is dependent upon phosphorylation of tyrosine 173 of the CD28 cytoplasmic tail, present in a YMNM motif. However,whether this phosphorylation is required for CD28 costimulation and whether or not phosphorylation of any of the other three tyrosines of the CD28 cytoplasmic tail (tyrosines 188, 191 and 200) is also important for CD28 induced responses is unclear. To address this we examined the ability of chimeric receptors, consisting of the extracellular plus transmembrane membrane domain of human CD8α linked to different mutated human CD28 cytoplasmic tails, to induce IL-2 secretion in Jurkat T leukemia cells in the presence of PMA and ionomycin. A receptor in which tyrosine 173 of the CD28 tail was mutated to phenylalanine was able to induce IL-2. By contrast, receptors which contained single tyrosine 188, 191 or 200 to phenylalanine substitutions were unable to induce IL-2. These results imply that in this system phosphorylation of tyrosine 173 and hence activation of PI3-kinase is not required for CD28 induced IL-2 secretion. Further, they imply that phosphorylation of each of tyrosines 188, 191 and 200 is necessary for this response. Despite an apparent requirement for phosphorylation of all three of these tyrosines, however, receptors which contain tyrosine only at positions 191 or 200 and a truncated receptor which does not contain tyrosine 200 induce normal IL-2. These last findings, therefore, illustrate the complexity of CD28 mediated activation signals.
Keywords:	controlled study; protein phosphorylation; human cell; protein domain; cd8 antigen; t lymphocyte; t-lymphocytes; interleukin 2; amino acid substitution; enzyme activation; tyrosine; mutational analysis; phosphorylation; phosphatidylinositol 3 kinase; t lymphocyte receptor; phosphotransferases (alcohol group acceptor); 1-phosphatidylinositol 3-kinase; cytoplasm; t cell leukemia; cd28 antigen; antigens, cd28; interleukin-2; phenylalanine; jurkat cells; phorbol 13 acetate 12 myristate; phosphatidylinositol 3-kinase; cd28; costimulation; cell signaling; ionomycin; humans; human; priority journal; article
Journal Title:	Tissue Antigens
Volume:	48
Issue:	4
ISSN:	0001-2815
Publisher:	Wiley-Blackwell Publishing, Inc.
Date Published:	1996-10-01
Start Page:	255
End Page:	264
Language:	English
PUBMED:	8946678
PROVIDER:	scopus
DOI:	10.1111/j.1399-0039.1996.tb02643.x
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0029910720&partnerID=40&md5=b40b9db01e1a51aa9c6d065400733645
Notes:	Article -- Export Date: 22 November 2017 -- Source: Scopus

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