The mitogen‐activated protein kinase signaling pathways: role in megakaryocyte differentiation

Revealing eltrombopags promotion of human megakaryopoiesis through AKT/ERK-dependent pathway activation

“…25 Of note, these different effects reflected different patterns of activation of AKT and ERK1/2 kinases, which are known to be crucial for the regulation of megakaryocyte maturation and the process of platelet production which occurs in healthy conditions. [33][34][35][40][41][42] In the present study we observed that eltrombopag sustained a concomitant phosphorylation of both AKT and ERK1/2 both in hematopoietic progenitors and mature megakaryocytes, while in our previous work romiplostim was shown to stimulate mainly megakaryocyte proliferation by increasing AKT phosphorylation only. 25 Overall, our studies on the effects of eltrombopag and romiplostim on in vitro human megakaryopoiesis suggest that these two drugs increase platelet output by different mechanisms: the former by stimulating increased megakaryocyte maturation and proplatelet formation, the latter by increasing mainly megakaryocyte proliferation without a correspondent parallel stimulation of megakary-…”

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

“…MEK1/2-ERK1/2 activation has been linked to mechanical stimulation-induced proliferation in diverse cell types, including chondrocytes (13,24,32). MEK1/2 activated ERK1/2, which functions as a final effector of signal transduction pathways and plays an essential role in cell proliferation, differentiation, and migration by directly activating transcription factors in the cytoplasm and nucleus (6,7,33). Ryan et al (9) reported that cyclic mechanical compression of articular cartilage induces chondrocyte proliferation by activation of the ERK1/2 pathway.…”

“…MEK1/2 and ERK1/2 exist in virtually all eukaryotic cells and control fundamental cellular functions (6)(7)(8). There is increasing evidence that MEK and ERK1/2 are involved in the regulation of chondrocyte proliferation, matrix synthesis, and migration in response to periodic mechanical stimulation (9)(10)(11)(12).…”

Domain 2 of uPAR regulates single-chain urokinase-mediated angiogenesis through β1-integrin and VEGFR2

“…LY-294002 inhibits PI3K, mTOR, DNA-dependent protein kinase, casein kinase 2, and Pim-1 (29). In cells of hematopoietic origin, inhibition of PI3K influences pERK1/2 expression through the sequential effects of phospholipase C-␥, Raf-1, and MEK (58). Stimulation of pERK1/2 expression by ScuPA is independent of pAkt (Ser 473 ) because in SIN1 Ϫ/Ϫ MEFs, p44/42 MAPK is phosphorylated in its absence (37).…”