Signaling through surface receptors in immune cells.

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The human IL-5R (hIL-5R) consists of two distinct polypeptide chains, alpha and beta which activates JAK1 and JAK2 and STAT5. We analyzed the interaction between hIL-5Ralpha and betac by immuno-precipitation using anti-hIL-5Ralpha and anti-betac mAbs. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated inTF-h5Ralpha. IL-5 stimulation induced the recruitment of betac to hIL-5Ralpha, although in the absence of IL-5 the subunits remained independent. JAK2 and JAK1 were associated with hIL-5Ralpha and betac, respectively. IL-S stimulation resulted in tyrosine phosphoryl-ation of JAK2, JAK1, betac, and STAT5. Moreover, IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and the betac phosphorylation. Furthermore, tyrosine phosphorylation of JAK1 depended on the activation of JAK2. The cytoplasmic stretch at position 346-387, containing the proline-rich region was necessary for JAK2 binding. These observations suggest that activation of hIL-5Ralpha associated JAK2 is indispensable for IL-5 signaling event.Bone-marrow derived mast cells adhered to fibronectin via VLA-5 (alpha5beta1) upon stimulation with steel factor (SLF) and FceRI cross-linking as well as PMA.SLF and PMA, but not FcepsilonRI cross-linking induced a diffusion of VLA-5 as well as drastic morphological changes. In contrast, only FcepsilonRI cross-linking increased affinity of VLA-5. We also showed PI 3-kinase as a critical affinity modulator by a specific inhibitor, wortmannin, and by introduction ofa constitutively active p110 subunit ofPI-3 kinase. Utilization of affinity or spatial modulation of VLA-5 caused differential effects on adhesion in the presence of physiological concentrations of soluble fibronectin. Our findings indicate that adhesion via VLA-5 are regulated physiologically by two mechanisms ; affinity modulation through PI 3-kinase and spatial modulation possibly through protein kinase C.