NEUROHYPOPHYSEAL PEPTIDES STIMULATE THE PHOSPHORYLATION OF PRE-T CELLFOCAL ADHESION KINASES

Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the o uter surface of thymic epithelial cell plasma membrane from where OT i s able to interact with neurohypophysial peptide receptors expressed b y pre-T cells. Immature T cells bear a receptor of the V-1 subtype, wh ile OT receptors are predominantly expressed by cytotoxic CD8+ lymphoc ytes. In both T cell types, neurohypophysial peptide receptors transdu ce OT via the phosphoinositide pathway. Protein tyrosine phosphorylati on is an early event of T cell activation. Western blots of murine pre -T cells (RL12-NP line) proteins probed with anti-phosphotyrosine (PY- 20) revealed a great number of proteins the phosphorylation of which i ncreased either with OT or vasopressin treatment. Two were immunopreci pitated with anti-focal adhesion kinase (FAK) mAb 2A7 and were identif ied one as p125(FAK) and the other as a coprecipitating 130-kDa protei n. The p125(FAK) is connected to the Ras/MAPK pathway and is also impl icated in TCR/CD3 signalling in T cell. Another protein phosphorylated by OT in RL12-NP was identified as paxillin, a 68-kDa protein localis ed at focal adhesion sites and associated with p125(FAK). These result s indicate that phosphorylation of focal adhesion kinase may be induce d in pre-T cell by thymic OT.