Regulation of Phospholipase C-γ1 by Profilin and Tyrosine Phosphorylation

Goldschmidt‐Clermont, Pascal J.; Kim, Jae Won; Machesky, Laura M.; Rhee, Sue Goo; Pollard, Thomas D.

doi:10.1126/science.1848725

Cited by 525 publications

(271 citation statements)

References 25 publications

Supporting

Mentioning

263

Contrasting

Unclassified

Order By: Relevance

“…Tyrosine phosphorylation of PLCg has been suggested to mediate its catalytic activation [46]. PLCg2 was rapidly tyrosine phosphorylated in both wild-type and Btk M B cells and the phosphorylation was maintained throughout the time period of the experiment (20 min) in both cell types (Fig.…”

Section: Bcr-induced Plcg Tyrosine Phosphorylation Is Normal In Btk Mmentioning

confidence: 93%

Reduced Formation of Phosphatidic Acid upon B‐Cell Receptor Triggering of Mouse B‐Lymphocytes Lacking Bruton's Tyrosine Kinase

2000

View full text Add to dashboard Cite

Btk de®cient (Btk M ) mouse B-lymphocytes do not proliferate when stimulated with anti-immunoglobulin (anti-Ig) antibodies. In order to characterize the molecular basis of this unresponsiveness we have compared early signal transduction pathways triggered by ligating the B cell antigen receptor (BCR) of puri®ed resting B cells from normal C57BL/6 (wild-type) and Btk M mice on C57BL/6 background. BCR-induced signalling events that occur during the ®rst few minutes of activation, such as bulk tyrosine phosphorylations, mitogenactivated protein kinase (MAPK) activation, PI3-kinase dependent PKB/Akt kinase phosphorylation/activation and PLCg2 tyrosine phosphorylation are comparable in wild type and Btk M B cells. However, the initial extracellular calcium in¯ux is reduced and the BCR-induced accumulation of phosphatidic acid (PA) display a more transient pro®le in the Btk M cells. BCR ligation did not induce detectable phosphatidyl-choline PLD activity, suggesting that the reduced PA is owing to a reduction in the phospho-inositide hydrolysis. These ®ndings further support the notion that the proliferative defect of Btk de®cient mouse B cells in response to anti-immunoglobulin stimulation stems from a failure to sustain phospholipase-dependent signalling.

show abstract

Section: Bcr-induced Plcg Tyrosine Phosphorylation Is Normal In Btk Mmentioning

confidence: 93%

Reduced Formation of Phosphatidic Acid upon B‐Cell Receptor Triggering of Mouse B‐Lymphocytes Lacking Bruton's Tyrosine Kinase

2000

View full text Add to dashboard Cite

show abstract

“…PLC␤ 1 activity was studied in the pres- PIP 2 Binding to Tubulin-In order to clarify the inhibitory action of tubulin on PLC␤ 1 , the interaction between tubulin and the PLC␤ 1 substrate, PIP 2 , was studied. It has been shown previously that phosphatidylinositol inhibits microtubule assembly (34) and that the binding of profilin (an actin-binding protein) to PIP 2 micelles inhibits PLC␥ 1 -directed PIP 2 hydrolysis (35). To test the possibility that tubulin binds PIP 2 , a gel filtration assay was performed.…”

Section: Resultsmentioning

confidence: 99%

Tubulin, Gq, and Phosphatidylinositol 4,5-Bisphosphate Interact to Regulate Phospholipase Cβ1 Signaling

Popova

Garrison

Rhee

et al. 1997

Journal of Biological Chemistry

Self Cite

134

View full text Add to dashboard Cite

The cytoskeletal protein, tubulin, has been shown to regulate adenylyl cyclase activity through its interaction with the specific G protein ␣ subunits, G␣ s or G␣ i1 . Tubulin activates these G proteins by transferring GTP and stabilizing the active nucleotide-bound G␣ conformation. To study the possibility of tubulin involvement in G␣ q -mediated phospholipase C␤ 1 (PLC␤ 1 ) signaling, the m 1 muscarinic receptor, G␣ q , and PLC␤ 1 were expressed in Sf9 cells. A unique ability of tubulin to regulate PLC␤ 1 was observed. Low concentrations of tubulin, with guanine nucleotide bound, activated PLC␤ 1 , whereas higher concentrations inhibited the enzyme. Interaction of tubulin with both G␣ q and PLC␤ 1 , accompanied by guanine nucleotide transfer from tubulin to G␣ q , is suggested as a mechanism for the enzyme activation. The PLC␤ 1 substrate, phosphatidylinositol 4,5-bisphosphate, bound to tubulin and prevented microtubule assembly. This observation suggested a mechanism for the inhibition of PLC␤ 1 by tubulin, since high tubulin concentrations might prevent the access of PLC␤ 1 to its substrate. Activation of m 1 muscarinic receptors by carbachol relaxed this inhibition, probably by increasing the affinity of G␣ q for tubulin. Involvement of tubulin in the articulation between PLC␤ 1 signaling and microtubule assembly might prove important for the intracellular governing of a broad range of cellular events.

show abstract

“…Assay of PLC Activity-PLC activity was assayed using [ 3 H]PIP 2 -containing liposomes as substrate as described previously by Goldschmidt-Clermont et al (14).…”

Section: Methodsmentioning

confidence: 99%

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Venema

et al. 1998

Journal of Biological Chemistry

100

View full text Add to dashboard Cite

An early event in signaling by the G-protein-coupled angiotensin II (Ang II) AT 1 receptor in vascular smooth muscle cells is the tyrosine phosphorylation and activation of phospholipase C␥1 (PLC␥1). In the present study, we show that stimulation of this event by Ang II in vascular smooth muscle cells is accompanied by binding of PLC␥1 to the AT 1 receptor in an Ang II-and tyrosine phophorylation-dependent manner. The PLC␥1-AT 1 receptor interaction appears to depend on phosphorylation of tyrosine 319 in a YIPP motif in the C-terminal intracellular domain of the AT 1 receptor and binding of the phosphorylated receptor by the most C-terminal of two Src homology 2 domains in PLC␥1. PLC␥1 thus binds to the same site in the receptor previously identified for binding by the SHP-2 phosphotyrosine phosphatase⅐JAK2 tyrosine kinase complex. A single site in the C-terminal tail of the AT 1 receptor can, therefore, be bound in a ligand-dependent manner by two different downstream effector proteins. These data demonstrate that G-protein-coupled receptors can physically associate with intracellular proteins other than G proteins, creating membrane-delimited signal transduction complexes similar to those observed for classic growth factor receptors.Growth factor receptors belong to a family of receptors that contain an extracellular ligand binding domain, a single transmembrane portion, and a large intracellular tyrosine kinase catalytic domain. Ligand-induced receptor autophosphorylation promotes the interaction of the intracellular domains of the receptors with a number of downstream effector proteins or enzymes. Typically, these proteins contain one or more domains known as Src homology 2 (SH2) 1 domains. Among these SH2 domain-containing proteins are phosphoinositide-specific phospholipase C␥ (PLC␥), the 85-kDa subunit of phosphatidylinositol 3-kinase, GTPase-activating proteins, growth factor receptor binding protein 2, the phosphotyrosine phosphatase SHP-2, and members of the nonreceptor Src family of tyrosine kinases (1, 2). Autophosphorylation of growth factor receptors occurs on defined tyrosine residues. These phosphorylated residues function to initiate cellular signaling cascades by acting as high affinity binding sites for the SH2 domains of various effector proteins. The selectivity of the receptor-effector interaction is determined, not only by the phosphorylated tyrosine residue in the receptor but also by the three amino acids Cterminal to the phosphorylated tyrosine and by the structure of the SH2 domain of the interacting protein. For example, one of the identified sites for binding of the SH2 domains of PLC␥1 to the platelet-derived growth factor ␣ and ␤ receptors is a YIPP motif present in the receptors at residues 1018 -1021 and 1021-1024, respectively. Phosphorylation of tyrosines 1018 and 1021 in these motifs promotes binding of PLC␥1 to the platelet-derived growth factor receptor and tyrosine phosphorylation and activation of the enzyme (3, 4).Another family of cell surface receptors are the G-protein...

show abstract

Regulation of Phospholipase C-γ1 by Profilin and Tyrosine Phosphorylation

Cited by 525 publications

References 25 publications

Reduced Formation of Phosphatidic Acid upon B‐Cell Receptor Triggering of Mouse B‐Lymphocytes Lacking Bruton's Tyrosine Kinase

Reduced Formation of Phosphatidic Acid upon B‐Cell Receptor Triggering of Mouse B‐Lymphocytes Lacking Bruton's Tyrosine Kinase

Tubulin, Gq, and Phosphatidylinositol 4,5-Bisphosphate Interact to Regulate Phospholipase Cβ1 Signaling

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Contact Info

Product

Resources

About