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Abstract-Reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ) activate intracellular signal transduction pathways implicated in the pathogenesis of cardiovascular disease. H 2 O 2 is a mitogen for rat vascular smooth muscle cells (VSMCs), and protein tyrosine phosphorylation is a critical event in VSMC mitogenesis. Therefore, we investigated whether the mitogenic effects of H 2 O 2 , such as stimulation of extracellular signal-regulated kinase (ERK)2, are mediated via activation of cytoplasmic Janus tyrosine kinases (JAKs). JAK2 was activated rapidly in VSMCs treated with H 2 O 2 , and signal transducers and activators of transcription (STAT) STAT1 and STAT3 were tyrosine-phosphorylated and translocated to the nucleus in a JAK2-dependent manner. A ccumulating evidence supports a critical role for oxidative stress in the pathogenesis of atherosclerosis, cancer, and other human diseases. 1 High levels of reactive oxygen species (ROS) damage DNA and inactivate proteins, 2 resulting in chronic cellular dysfunction. Many cell types have also harnessed ROS, albeit in lower concentrations, as intracellular signaling molecules to mediate growth factor and cytokine responses. 3,4 Modulation of growth responses by ROS has been demonstrated in a number of cell types, including vascular smooth muscle cells (VSMCs). 5,6 Stimulation of VSMC proliferation by ROS is thought to be a critical step in atherosclerotic lesion formation. 7 Tyrosine phosphorylation of cellular proteins and the consequent induction of transcription of early-response genes are key determinants of cell growth and differentiation in response to mitogenic signaling. 8 VSMC mitogens such as platelet-derived growth factor and epidermal growth factor activate receptor protein tyrosine kinases on binding, which stimulate intracellular signaling pathways that result in mitogen-activated protein kinase activation. 9,10 Other mitogens, such as thrombin and angiotensin II, activate G proteincoupled receptors that do not possess intrinsic tyrosine kinase activity but require tyrosine phosphorylation events to induce mitogenesis. [11][12][13] The necessary role for protein tyrosine phosphorylation in mitogenesis elicited by thrombin and ROS indicates that these mitogens may utilize cytoplasmic protein tyrosine kinases in their signaling cascade. Forming 1 such group of tyrosine kinases are Janus kinases (JAKs), which along with their substrates, signal transducers and activators of transcription (STATs), have hitherto been characterized as essential mediators of cytokine and polypeptide hormone-induced signaling. 8,14 Members of the JAK/STAT pathway mediate at least some biological effects of angiotensin II, 15 plateletderived growth factor-BB, 15,16 and endothelial growth factor. 17 Activation of the JAK/STAT pathway has also been observed in response to generation of intracellular ROS 18 and exogenous hydrogen peroxide (H 2 O 2 ). 19 On phosphorylation by JAKs of tyrosine residues, activated STAT dimers translocate to the nucleus to transactivate tar...

BackgroundZinc (Zn) and iron (Fe) are essential micronutrients for plant growth and development, their deficiency or excess severely impaired physiological and biochemical reactions of plants. Therefore, a tightly controlled zinc and iron uptake and homeostasis network has been evolved in plants. The Zinc-regulated transporters, Iron-regulated transporter-like Proteins (ZIP) are capable of uptaking and transporting divalent metal ion and are suggested to play critical roles in balancing metal uptake and homeostasis, though a detailed analysis of ZIP gene family in maize is still lacking.ResultsNine ZIP-coding genes were identified in maize genome. It was revealed that the ZmZIP proteins share a conserved transmembrane domain and a variable region between TM-3 and TM-4. Transiently expression in onion epidermal cells revealed that all ZmZIP proteins were localized to the endoplasmic reticulum and plasma membrane. The yeast complementation analysis was performed to test the Zn or Fe transporter activity of ZmZIP proteins. Expression analysis showed that the ZmIRT1 transcripts were dramatically induced in response to Zn- and Fe-deficiency, though the expression profiles of other ZmZIP changed variously. The expression patterns of ZmZIP genes were observed in different stages of embryo and endosperm development. The accumulations of ZmIRT1 and ZmZIP6 were increased in the late developmental stages of embryo, while ZmZIP4 was up-regulated during the early development of embryo. In addition, the expression of ZmZIP5 was dramatically induced associated with middle stage development of embryo and endosperm.ConclusionsThese results suggest that ZmZIP genes encode functional Zn or Fe transporters that may be responsible for the uptake, translocation, detoxification and storage of divalent metal ion in plant cells. The various expression patterns of ZmZIP genes in embryo and endosperm indicates that they may be essential for ion translocation and storage during differential stages of embryo and endosperm development. The present study provides new insights into the evolutionary relationship and putative functional divergence of the ZmZIP gene family during the growth and development of maize.