Structural and functional analysis of the putative inositol 1,3,4, 5-tetrakisphosphate receptors GAP1(IP4BP) and GAP1(m).
Previously we have purified and cloned a high affinity isomerically specific inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4)-binding protein which, because it is clearly a member of the GAP1 family of Ras GTPase-activating proteins (GAP), we have termed GAP1(IP4BP). Here we show that expressed full-length GAP1(IP4BP) binds Ins(1,3,4, 5)P4 with an affinity and specificity similar to that of the originally purified protein, a binding activity which is dependent on a functional PH/Btk domain. Furthermore, we highlight a fundamental distinction between GAP1(IP4BP) and its homologue GAP1(m), namely that both proteins function as Ras GAPs but only GAP1(IP4BP) displays Rap GAP activity.
Bottomley
J R
JR
School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom.
Reynolds
J S
JS
Lockyer
P J
PJ
Cullen
P J
PJ
D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D007295:Inositol Phosphates / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins
D017931:DNA Primers; D007295:Inositol Phosphates; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C061107:inositol-1,3,4,5-tetrakisphosphate receptor; D020703:ras GTPase-Activating Proteins; C081655:inositol-1,3,4,5-tetrakisphosphate