Ajuba, a novel LIM protein, interacts with Grb2, augments mitogen-activated protein kinase activity in fibroblasts, and promotes meiotic maturation of Xenopus oocytes in a Grb2-and Ras-dependent manner

LIM domain-containing proteins contribute to cell fate determination, the r egulation of cell proliferation and differentiation, and remodeling of the cell cytoskeleton. These proteins can be found in the cell nucleus, cytopla sm, or both. Whether and how cytoplasmic LIM proteins contribute to the cel lular response to extracellular stimuli is an area of active investigation. We have identified and characterized a new LIM protein, Ajuba. Although pr edominantly a cytosolic protein, in contrast to other like proteins, it did not localize to sites of cellular adhesion to extracellular matrix or inte ract with the actin cytoskeleton, Removal of the pre-LIM domain of Ajuba, i ncluding a putative nuclear export signal, fed to an accumulation of the LI M domains in the cell nucleus. The pre-LIM domain contains two putative pro line-rich SH3 recognition motifs, Ajuba specifically associated with Grb2 i n vitro and in vivo. The interaction between these proteins was mediated by either SH3 domain of Grb2 and the N-terminal proline-rich pre-LIM domain o f Ajuba. In fibroblasts expressing Ajuba mitogen-activated protein kinase a ctivity persisted despite serum starvation and upon serum stimulation gener ated levels fivefold higher than that seen in control cells. Finally, when Ajuba was expressed in fully developed Xenopus oocytes, it promoted meiotic maturation in a Grb2- and Ras-dependent manner.