Several related isoforms of p^38MAPK have been identified and cloned in many species. While they all contain the dual phosphorylation motif TGY, the expression of these isoforms is not ubiquitous. p38 and 2 are ubiquitously expressed while p38 and appear to have more restricted expression. Since there is evidence for selective activation by upstream kinases and selective preference for downstream substrates, the functions of these conserved proteins is still incompletely understood. We have demonstrated that the renal mesangial cell expresses the mRNA for all the isoforms of p^38MAPK, with p38 mRNA expressed at the highest level, followed by p38 and the lowest levels of expression by p382 and . To determine the functional effects of these proteins on IL-1-induced iNOS expression, we transduced TAT-p38 chimeric proteins into renal mesangial cells and assessed the effects of wild type and mutant p38 isoforms on ligand induced iNOS expression. We show that while p38 and had minimal effects on iNOS expression, p38 and 2 do. p38 mutant and p382 wild type dose dependently inhibited IL-1-induced iNOS expression. This data suggests that p38 and 2 have reciprocal effects on iNOS expression in the mesangial cell and these observations may have important consequences for the development of selective inhibitors targeting the p^38MAPK family of proteins.