Previously, Rab5 was shown to transduce cell-survival signals by facilitating vesicular translocation to the nucleus of multiple signaling kinases in neurons, including Akt and Erk (Delcroix et al., 2003).
The PTHRP-R can couple to multiple signalling systems, including Ca2+/protein kinase C, cAMP and Ras/ERK pathways (Carpio et al, 2001; Miao et al, 2001).
We therefore tested whether any of multiple signaling proteins, mainly kinases, were activated using a specific, semi-quantitative method to identify them with Kinetworks™ screens.
Activated JAK2 kinase stimulates multiple signalling pathways in erythrocytic precursor cells (Huang et al, 2001; Jelkmann et al, 2008).
15 Recently, LPP was identified as a substrate of the protein-tyrosine phosphatase 1B, a negative regulator of multiple signalling pathways downstream of receptor tyrosine kinases and functionally linked to Ras signalling.
mTOR is an evolutionarily conserved serine/threonine protein kinase which integrates multiple signalling pathways regulating gene expression involved in metabolism, cell survival, and cell proliferation [15].
Insulin controls glucose metabolism via multiple signalling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway in muscle and adipose tissue.
Increased ERBB2/3 alters multiple signaling pathways, including kinase signaling, and, thus, impairs normal cellular control mechanisms, giving rise to malignant tumor cell transformation [ 42].
In certain therapeutic areas such as oncology, the efficacy of a drug often depends on its ability to specifically bind to multiple targets and elicit polypharmacological effects (i.e., interference with multiple signaling pathways), with kinase inhibitors being a prime example.
