CALCIUM-DEPENDENT SIGNALING PATHWAYS IN T-CELLS - POTENTIAL ROLE OF CALPAIN, PROTEIN-TYROSINE-PHOSPHATASE 1B, AND P130(CAS) IN INTEGRIN-MEDIATED SIGNALING EVENTS

Engagement of beta 1 integrin receptors initiates an increase in intra cellular calcium concentrations in T cells, potentially affecting calc ium-sensitive signaling pathways. The calcium-activated cysteine prote ase, calpain, regulates a variety of cell functions by calcium-depende nt limited proteolysis. To investigate the function of calpain in T ce lls, we sought to determine the role of this protease in calcium-depen dent signaling events, Subsequent to elevations in intracellular calci um concentrations induced by ionomycin or adherence to fibronectin, ca lpain activity translocated to the cytoskeletal/membrane fraction of T cells. In addition, stimulation of T cells with these agents initiate d the proteolytic cleavage of protein tyrosine phosphatase 1B by calpa in. Enzymatic cleavage of protein tyrosine phosphatase 1B occurs near the endoplasmic reticulum-targeting sequence and results in the genera tion of an enzymatically active form of the phosphatase. Furthermore, we show that both the native and the cleaved forms of protein tyrosine phosphatase 1B interact with p130(Cas) in T cells, This interaction m ay serve to relocate protein tyrosine phosphatase 1B to sites of focal contact resulting in potential interactions with substrates previousl y inaccessible to the endoplasmic reticulum-associated phosphatase. Th us, we describe a novel calcium-dependent signaling pathway in T cells that may mediate signals generated by beta 1 integrin adherence to th e extracellular matrix.