The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor gamma-chain and linker for activitor of T cells (LAT) in platelets stimulated by collagen and convulxin.
There is extensive evidence to show that phosphatidylinositol 3-kinase plays an important role in signaling by the immune family of receptors, which has recently been extended to include the platelet collagen receptor, glycoprotein VI. In this report we present two potential mechanisms for the regulation of this enzyme on stimulation of platelets by collagen. We show that on stimulation with collagen, the regulatory subunit of phosphatidylinositol 3-kinase associates with the tyrosine-phosphorylated form of the adapter protein linker for activator of T Cells (LAT) and the tyrosine-phosphorylated immunoreceptor tyrosine-based activation motif of the Fc receptor gamma-chain (a component of the collagen receptor complex that includes glycoprotein VI). The associations of the Fc receptor gamma-chain and LAT with p85 are rapid and supported by the Src-homology 2 domains of the regulatory subunit. We did not obtain evidence to support previous observations that the regulatory subunit of phosphatidylinositol 3-kinase is regulated through association with the tyrosine kinase Syk. The present results provide a molecular basis for the regulation of the p85/110 form of phosphatidylinositol 3-kinase by GPVI, the collagen receptor that underlies activation.
Gibbins
J M
JM
School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berkshire, RG6 6AJ, United Kingdom. j.m.gibbins@rdg.ac.uk
Briddon
S
S
Shutes
A
A
van Vugt
M J
MJ
van de Winkel
J G
JG
Saito
T
T
Watson
S P
SP
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000097:blood*; D003094:Collagen / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000302:isolation & purification / Q000494:pharmacology*; D017839:Crotalus; D006801:Humans; D066298:In Vitro Techniques; D037181:Lectins, C-Type; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000378:metabolism*; D010748:Phosphopeptides / Q000737:chemistry / Q000494:pharmacology; D010750:Phosphoproteins / Q000097:blood*; D017452:Receptors, IgG / Q000737:chemistry / Q000502:physiology*; D012701:Serotonin / Q000097:blood; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003435:Crotalid Venoms; C110810:LAT protein, human; C491734:Lat protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D010446:Peptide Fragments; D010748:Phosphopeptides; D010750:Phosphoproteins; D017452:Receptors, IgG; D012701:Serotonin; C028890:convulxin; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases