Protein kinases as mediators of fluid shear stress stimulated signal transduction in endothelial cells: A hypothesis for calcium-dependent and calcium-independent events activated by flow

Berk, Bradford C.; Corson, Marshall A.; Peterson, Timothy E.; Tseng, Hennessey

doi:10.1016/0021-9290(95)00092-5

Cited by 140 publications

(88 citation statements)

References 81 publications

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“…Upon phosphorylation, FAK contributes to MAPK activation via interaction with c-src, Grb2, and the small GTPase Ras (Schlaepfer et al, 1997(Schlaepfer et al, , 1998(Schlaepfer et al, , 1999. This is significant since MAPK activation is also one of the effectors of oscillatory flow in bone cells (You et al, 2001) and this pathway has been observed in response to fluid flow in endothelial cells (Berk et al, 1995;Ishida et al, 1996;Li et al, 1997). It is also notable that FAK activation has been observed to cause intracellular calcium mobilization via activation of the γ1 isoform of PLC (the only SH2 containing isoform known).…”

Section: Integrins and Integrin Associated Proteinsmentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

385

296

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Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

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Section: Integrins and Integrin Associated Proteinsmentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

385

296

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“…PKA mediates several of the effects of the elevated levels of cAMP in the cells and has been reported to both activate and inhibit the ERK1/2 signaling pathway either directly or through the activation of Rap1 (45). Although both PKA and PKC can modulate the activity of ERK1/2 pathways by phosphorylation of Raf kinases, PKA preferentially targets B-Raf, whereas PKC alters the activity of the Raf-1 isoform (7,45,54,57).…”

Section: Fig 10mentioning

confidence: 99%

Distinct Signaling Pathways Are Activated in Response to Mechanical Stress Applied Axially and Transversely to Skeletal Muscle Fibers

Kumar

Chaudhry

Reid

et al. 2002

Journal of Biological Chemistry

111

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In the diaphragm muscle we tested the hypothesis that MAP kinase signaling pathways are activated by mechanical stress and such signaling pathways are dependent on the direction in which mechanical stress is applied. Although equal magnitudes of mechanical stress were applied axially and transversely a greater level of activation of ERK1/2, p38, Raf-1, p90 RSK, Elk-1, and the DNA binding activity of AP-1 transcription factor was produced when the muscle was stretched transversely than when stretched axially. A significant up-regulation in protein tyrosine phosphorylation was observed in axially or transversely loaded diaphragm muscles and the activation of ERK1/2 was completely inhibited by genistein (protein-tyrosine kinase inhibitor). Pretreatment of muscles with wortmannin (phosphoinositide 3-kinase inhibitor), TMB-8 (antagonist of intracellular calcium release), GF109203X (PKC inhibitor), or PD98059 (MEK1/2 inhibitor) blocked the activation of ERK1/2 kinases in response to axial but not to transverse loading. On the other hand, pretreatment of muscles with protein kinase A inhibitors H-7 and KT5720 completely suppressed the activation of ERK1/2 in response to transverse loading only. Taken together with the alterations of MAP kinases and the findings of elevations of downstream transcription targets, our data are consistent with two distinct MAP kinase signal transduction pathways in response to mechanical stress.

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“…It is well recognized that when ECs are subjected to hemodynamic forces, Ca 2ϩ mobilization plays an essential role in endothelial responses (20,35). When ECs are under hemodynamic treatment, a rapid increase of [Ca 2ϩ ] i (35,36), inositol triphosphate and DAG (17) occurs. DAG is produced from hydrolysis of PI and PC (17).…”

Section: Sequential Activation Of Pkc-␣ and -⑀ Contributes To Strainimentioning

confidence: 99%

Sequential Activation of Protein Kinase C (PKC)-α and PKC-ε Contributes to Sustained Raf/ERK1/2 Activation in Endothelial Cells under Mechanical Strain

Cheng

Wung

Chao

et al. 2001

Journal of Biological Chemistry

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Endothelial cells (ECs) are constantly subjected to hemodynamic forces including cyclic pressure-induced strain. The role of protein kinase C (PKC) in cyclic strain-treated ECs was studied. PKC activities were induced as cyclic strain was initiated. Cyclic strain to ECs caused activation of PKC-␣ and -⑀. The translocation of PKC-␣ and -⑀ but not PKC-␤ from the cytosolic to membrane fraction was observed. An early transient activation of PKC-␣ versus a late but sustained activation of PKC-⑀ was shown after the onset of cyclic strain. Consistently, a sequential association of PKC-␣ and -⑀ with the signaling molecule Raf-1 was shown. ECs treated with a PKC inhibitor (calphostin C) abolished the cyclic strain-induced Raf-1 activation. ECs under cyclic strain induced a sustained activation of extracellular signalregulated protein kinases (ERK1/2), which was inhibited by treating ECs with calphostin C. ECs treated with a specific Ca 2؉ -dependent PKC inhibitor (Go 6976) showed an inhibition in the early phase of ERK1/2 activation but not in the late and sustained phase. ECs transfected with the antisense to PKC-␣, the antisense to PKC-⑀, or the inhibition peptide to PKC-⑀ reduced strain-induced ERK1/2 phosphorylation in a temporal manner. PKC-␣ mediated mainly the early ERK1/2 activation, whereas PKC-⑀ was involved in the sustained ERK1/2 activation. Strained ECs increased transcriptional activity of Elk1 (an ERK1/2 substrate). ECs transfected with the antisense to each PKC isoform reduced Elk1 and monocyte chemotactic protein-1 promotor activity. Our findings conclude that a sequential activation of PKC isoform (␣ and ⑀) contribute to Raf/ERK1/2 activation, and PKC-⑀ appears to play a key role in endothelial adaptation to hemodynamic environment.

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Protein kinases as mediators of fluid shear stress stimulated signal transduction in endothelial cells: A hypothesis for calcium-dependent and calcium-independent events activated by flow

Cited by 140 publications

References 81 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

Distinct Signaling Pathways Are Activated in Response to Mechanical Stress Applied Axially and Transversely to Skeletal Muscle Fibers

Sequential Activation of Protein Kinase C (PKC)-α and PKC-ε Contributes to Sustained Raf/ERK1/2 Activation in Endothelial Cells under Mechanical Strain

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