It is well known that inositol 1,4,5-trisphosphate binding and release of calcium are mediated by the same protein. Several reports have indicated the location of the inositol 1,4,5-trisphosphate receptor in organelles other than endoplasmic reticulum. Immunocytochemical studies on the subcellular localization of 1,4,5-trisphosphate receptor in the Purkinje cells from two laboratories have given contradictory results regarding the nuclear location of this receptor. In this paper, a high-affinity inositol 1,4,5-[32P]trisphosphate binding site (Kd = 0.11 nM) on nuclei isolated from rat liver and devoid of any microsomal, mitochondrial, or plasma membrane constituents is documented. Furthermore, we present data demonstrating that inositol 1,4,5-trisphosphate is capable of releasing 45Ca2+ from the intact isolated liver nuclei. A rapid and transient release of calcium that was taken up by nuclei in the presence of ATP is observed. The role of inositol 1,4,5-trisphosphate in the coupling between cytoplasmic second messengers and nuclear events activated during signal transduction is postulated.Since the report (1) that inositol 1,4,5-trisphosphate (InsP3) releases calcium from nonmitochondrial intracellular stores, its role as a second messenger (2) for a multiplicity of neurotransmitters, hormones, and growth factors (3-5) has been documented. Specific InsP3 binding has been found in a variety of tissues, and the InsP3 receptor has been purified from rat (6) and mouse (7)

the use of Ca 2ϩ -sensitive fluorescent indicators. In particular it has shifted the emphasis from the long-term determination of Ca 2ϩ level to the study of short-term delays in the transmission of the cytosolic Ca 2ϩ waves to the nucleus. Cytosolic Ca 2ϩ waves depend upon the

There is growing evidence for the role of protein tyrosine phosphatases in controlling such fundamental cellular processes as growth and differentiation. Pervanadate is a potent inhibitor of protein tyrosine phosphatase which has been observed here to induce proliferation in C3H10T1/2 mouse fibroblasts. Pervanadate also translocated/activated p42/44 mitogen-activated protein (MAP) kinase to the cell nucleus. An almost similar pattern of nuclear p42/44 MAP kinase stimulation is seen with TPA. On the other hand, TPA treatment results in a rapid activation of cytosolic MAP kinase which declines with time. Thus pervanadate appears as a very useful tool for studying tyrosine phosphorylation.

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