Cyclin E/CDK2 also functions upstream, and is a regulator, of histone biosynthesis (reviewed in [ 4]); however, none of the earlier known cyclin E/CDK2 substrates serves downstream to promote histone biosynthesis.
Instead of serving as downstream effectors, some Aurora-A substrates and interacting proteins such as the microtubule-associated protein TPX2 [4], [4], the LIM domain-containing protein Ajuba [5] and the focal-adhesion protein PAK1 [6], play roles as upstream regulators that mediate Aurora-A kinase activity.
Potential factors connecting AT1R activation to the nucleus and therefore serving as downstream transmitters of the AT1R binding signal are the signaling kinases FRK, ERK, and JNK [ 19, 26, 28].
The observation that the Tak1 phenotype represents a mixture of BMP-associated phenotypes indicates that TAK1 serves an essential function downstream of multiple BMP family members.
Moreover, the Aurora-A activators PAK1, HEF and Ajuba are present at focal adhesions and serve as downstream effectors of integrin during the process of cell migration.
These results further support the likelihood that Eaf1 and Eaf2/U19 serve as downstream mediators of Wnt4a signaling, consistent with results obtained in Xenopus laevis [12].
The possibility that SOCS (suppressor of cytokine signaling) proteins, known as critical targets of IL-6 in liver, serve as downstream mediators in this dietary model of NASH needs to be investigated.
In yeast, the cleaved prenylated peptide serves a downstream signaling function (Chen et al. 1997; Boyartchuk and Rine 1998).
Insulin receptor substrates (IRS) serve as downstream messengers from activated cell surface receptors to numerous signaling pathway cascades including PI3K [ 33].
The magnitude of flow was considered 'high' when more than 19 homes were served just downstream by the water pipe at the sample location (n = 19).
