Src-family tyrosine kinases, phosphoinositide 3-kinase and Gab1 regulate extracellular signal-regulated kinase 1 activation induced by the type A endothelin-1 G-protein-coupled receptor

Bisotto, Sandra; Fixman, Elizabeth D.

doi:10.1042/bj3600077

Cited by 21 publications

(14 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, a member (PI3Kg) of the PI3 kinase family activates ERK as well as Akt (38). Tyrosine phosphorylation of Gab1, a Grb-2-associated binder, also plays a pivotal role in PI3 kinase-dependent ERK activation in response to endothelin-1 which activates G-protein-coupled receptor signaling cascades (39). On the contrary, Akt inhibits the Raf -MEK -ERK pathway in the course of myotube differentiation (40).…”

Section: Discussionmentioning

confidence: 99%

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Kang¹,

Song²,

Kang³

et al. 2003

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Insulin has well-known activities in controlling energy metabolism, cellular proliferation and biosynthesis of functional molecules to maintain a biological homeostasis. Recently, several studies have suggested that insulin may protect cells from apoptosis in different cell lines; however, little is known about the nature of its anti-apoptotic activity. In many clinical disorders, including type 2 diabetes mellitus, oxidative stress and the production of reactive oxygen species (ROS) is increased. With these facts as a background, we examined here whether insulin protects HepG2 cells from apoptosis by decreasing oxidative stress and, if so, which signaling steps are involved in this process. Methods: Intracellular DNA content, the degree of nuclear condensation or poly(ADP-ribose) polymerase hydrolysis was measured to verify the occurrence of apoptotic events. Caspase-3 activity and ROS accumulation within cells were also measured. Western blot analysis was performed to identify signaling molecules activated in response to insulin. Results: Serum starvation resulted in a marked accumulation of ROS, activation of caspase-3, and subsequent apoptotic cell death which were, in turn, markedly blocked by the addition of insulin. The anti-apoptotic activity of insulin was sensitive to blockade of two different signaling steps, activations of phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signal-regulated protein kinase (ERK). Conclusion: Insulin exerts an anti-apoptotic activity by suppressing the excessive accumulation of ROS within cells through signaling pathways including stimulation of PI3 kinase and ERK in HepG2 cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Kang¹,

Song²,

Kang³

et al. 2003

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…In addition, that SrcS17D is constitutively active suggest that it is not just being relocalized, but is activated as well. It is also possible that this phosphorylation may influence the binding of additional docking/adaptor proteins that influence both the activity of Src and choice of substrates (54,(57)(58)(59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

Gα and Gβγ Require Distinct Src-dependent Pathways to Activate Rap1 and Ras

Schmitt¹,

Stork

2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

The Src tyrosine kinase is necessary for activation of extracellular signal-regulated kinases (ERKs) by the ␤-adrenergic receptor agonist, isoproterenol. In this study, we examined the role of Src in the stimulation of two small G proteins, Ras and Rap1, that have been implicated in isoproterenol's signaling to ERKs. We demonstrate that the activation of isoproterenol of both Rap1 and Ras requires Src. In HEK293 cells, isoproterenol activates Rap1, stimulates Rap1 association with B-Raf, and activates ERKs, all via PKA. In contrast, the activation by isoproterenol of Ras requires G␤␥ subunits, is independent of PKA, and results in the phosphoinositol 3-kinase-dependent activation of AKT. Interestingly, ␤-adrenergic stimulation of both Rap1 and ERKs, but not Ras and AKT, can be blocked by a Src mutant (SrcS17A) that is incapable of being phosphorylated and activated by PKA. Furthermore, a Src mutant (SrcS17D), which mimics PKA phosphorylation at serine 17, stimulates Rap1 activation, Rap1/B-Raf association, and ERK activation but does not stimulate Ras or AKT. These data suggest that Rap1 activation, but not that of Ras, is mediated through the direct phosphorylation of Src by PKA. We propose that the ␤ 2 -adrenergic receptor activates Src via two independent mechanisms to mediate distinct signaling pathways, one through G␣ s to Rap1 and ERKs and the other through G␤␥ to Ras and AKT.

show abstract

“…Here, members of the epidermal growth factor family and the src-family of non-receptor tyrosine kinases are candidate tyrosine kinases (Della Rocca et al 1999, Hackel et al 1999, Bisotto & Fixman 2001.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of mitogenic and anti-apoptotic signaling by glucose-dependent insulinotropic polypeptide in beta(INS-1)-cells

Trümper

K²,

Hörsch³

2002

Journal of Endocrinology

182

101

View full text Add to dashboard Cite

Glucose-dependent insulinotropic polypeptide (GIP) acts as a glucose-dependent growth factor for -cells. Here we show that GIP and glucose also act synergistically as anti-apoptotic factors for -cells, using the welldifferentiated -cell line, INS-1. Mitogenic and anti-apoptotic signaling of GIP were dependent upon pleiotropic activation of protein kinase A (PKA)/cAMP regulatory element binder (CREB), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-kinase)/PKB signaling modules. The signaling modules activated by GIP were dependent on glucose metabolism and calcium influx and were tightly linked by multiple activating and inhibiting cross-talk. These interactions included: (i) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, (ii) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, (iii) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and (iv) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream. Furthermore, we demonstrated inhibition of CREB signaling by Ca 2+ / calmodulin kinase I/IV. These results indicated that GIP acts as a mitogenic and anti-apoptotic factor for -cells by pleiotropic activation of tightly linked signaling pathways in -cells.

show abstract

Src-family tyrosine kinases, phosphoinositide 3-kinase and Gab1 regulate extracellular signal-regulated kinase 1 activation induced by the type A endothelin-1 G-protein-coupled receptor

Cited by 21 publications

References 45 publications

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Gα and Gβγ Require Distinct Src-dependent Pathways to Activate Rap1 and Ras

Mechanisms of mitogenic and anti-apoptotic signaling by glucose-dependent insulinotropic polypeptide in beta(INS-1)-cells

Contact Info

Product

Resources

About