The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing.
We recently characterized a novel protein, GIT1, that interacts with G protein-coupled receptor kinases and possesses ADP-ribosylation factor (ARF) GTPase-activating protein activity. A second ubiquitously expressed member of the GIT protein family, GIT2, has been identified in data base searches. GIT2 undergoes extensive alternative splicing and exists in at least 10 and potentially as many as 33 distinct forms. The longest form of GIT2 is colinear with GIT1 and shares the same domain structure, whereas one major splice variant prominent in immune tissues completely lacks the carboxyl-terminal domain. The other 32 potential variants arise from the independent alternative splicing of five internal regions in the center of the molecule but share both the amino-terminal ARF GTPase-activating protein domain and carboxyl-terminal domain. Both the long and short carboxyl-terminal variants of GIT2 are active as GTPase-activating proteins for ARF1, and both also interact with G protein-coupled receptor kinase 2 and with p21-activated kinase-interacting exchange factors complexed with p21-activated kinase but not with paxillin. Cellular overexpression of the longest variant of GIT2 leads to inhibition of beta(2)-adrenergic receptor sequestration, whereas the shortest splice variant appears inactive. Although GIT2 shares many properties with GIT1, it also exhibits both structural and functional diversity due to tissue-specific alternative splicing.
Premont
R T
RT
Departments of Medicine and Biochemistry, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA. richard.premont@duke.edu
Claing
A
A
Vitale
N
N
Perry
S J
SJ
Lefkowitz
R J
RJ
D020727:ADP-Ribosylation Factors / Q000235:genetics* / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000244:Adenosine Diphosphate / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D016415:Sequence Alignment
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D000244:Adenosine Diphosphate; D020727:ADP-Ribosylation Factors