Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction.

@article{citeulike:2481490, abstract = {The Raf kinase inhibitory protein 1 (RKIP-1) and its orthologs are conserved throughout evolution and widely expressed in eukaryotic organisms. In its non-phosphorylated form RKIP-1 negatively regulates the Raf/MEK/ERK pathway by interfering with the activity of Raf-1. In its phosphorylated state, RKIP-1 dissociates from Raf-1 and inhibits GRK-2, a negative regulator of G-protein coupled receptors (GPCRs). Available data indicate that the phosphorylation of RKIP-1 by PKC can stimulate both the Raf/MEK/ERK and GPCR pathways. RKIP-1 has also been implicated as a negative regulator of the NF-kappaB pathway. Recent studies have shown that phosphorylated RKIP-1 binds to the centrosomal and kinetochore regions of metaphase chromosomes, where it may be involved in regulating the partitioning of chromosomes and the progression through mitosis. The collective evidence indicates that RKIP-1 regulates the activity and mediates the crosstalk between several important cellular signaling pathways. A variety of ablative interventions suggest that reduced RKIP-1 function may influence metastasis, angiogenesis, resistance to apoptosis, and genome integrity. Attenuation of RKIP-1 may also affect cardiac and neurological functions, spermatogenesis, sperm decapacitation, and reproductive behavior. In this review, the role of RKIP-1 in cellular signaling, and especially its functions revealed using a mouse knockout model, are discussed.}, address = {Department of Molecular Biology Cell Biology and Biochemistry, Brown University, Providence, RI 02912, United States. Jan\_Klysik@Brown.edu}, author = {Klysik, J. and Theroux, S. J. and Sedivy, J. M. and Moffit, J. S. and Boekelheide, K. }, citeulike-article-id = {2481490}, doi = {10.1016/j.cellsig.2007.07.003}, issn = {0898-6568}, journal = {Cell Signal}, month = {January}, number = {1}, pages = {1--9}, posted-at = {2008-03-07 03:08:09}, priority = {2}, title = {Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction.}, url = {http://dx.doi.org/10.1016/j.cellsig.2007.07.003}, volume = {20}, year = {2008} }

TY - JOUR ID - citeulike:2481490 L3 - citeulike-article-id:2481490 TI - Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction. JF - Cell Signal VL - 20 IS - 1 SP - 1 EP - 9 AD - Department of Molecular Biology Cell Biology and Biochemistry, Brown University, Providence, RI 02912, United States. Jan_Klysik@Brown.edu SN - 0898-6568 N2 - The Raf kinase inhibitory protein 1 (RKIP-1) and its orthologs are conserved throughout evolution and widely expressed in eukaryotic organisms. In its non-phosphorylated form RKIP-1 negatively regulates the Raf/MEK/ERK pathway by interfering with the activity of Raf-1. In its phosphorylated state, RKIP-1 dissociates from Raf-1 and inhibits GRK-2, a negative regulator of G-protein coupled receptors (GPCRs). Available data indicate that the phosphorylation of RKIP-1 by PKC can stimulate both the Raf/MEK/ERK and GPCR pathways. RKIP-1 has also been implicated as a negative regulator of the NF-kappaB pathway. Recent studies have shown that phosphorylated RKIP-1 binds to the centrosomal and kinetochore regions of metaphase chromosomes, where it may be involved in regulating the partitioning of chromosomes and the progression through mitosis. The collective evidence indicates that RKIP-1 regulates the activity and mediates the crosstalk between several important cellular signaling pathways. A variety of ablative interventions suggest that reduced RKIP-1 function may influence metastasis, angiogenesis, resistance to apoptosis, and genome integrity. Attenuation of RKIP-1 may also affect cardiac and neurological functions, spermatogenesis, sperm decapacitation, and reproductive behavior. In this review, the role of RKIP-1 in cellular signaling, and especially its functions revealed using a mouse knockout model, are discussed. AU - Klysik, J AU - Theroux, SJ AU - Sedivy, JM AU - Moffit, JS AU - Boekelheide, K PY - 2008/01// UR - http://dx.doi.org/10.1016/j.cellsig.2007.07.003 ER -