The Roco protein family: a functional perspective.
In this review, we discuss the evolutionary, biochemical, and functional data available for members of the Roco protein family. They are characterized by having a conserved supradomain that contains a Ras-like GTPase domain, called Roc, and a characteristic COR (C-terminal of Roc) domain. A kinase domain and diverse regulatory and protein-protein interaction domains are also often found in Roco proteins. First detected in the slime mold Dictyostelium discoideum, they have a broad phylogenetic range, being present in both prokaryotes and eukaryotes. The functions of these proteins are diverse. The best understood are Dictyostelium Rocos, which are involved in cell division, chemotaxis, and development. However, this family has received extensive attention because mutations in one of the human Roco genes (LRRK2) cause familial Parkinson disease. Other human Rocos are involved in epilepsy and cancer. Biochemical data suggest that Roc domains are capable of activating kinase domains intramolecularly. Interestingly, some of the dominant, disease-causing mutations in both the GTPase and kinase domains of LRRK2 increase kinase activity. Thus, Roco proteins may act as stand-alone transduction units, performing roles that were thought so far to require multiple proteins, as occur in the Ras transduction pathway.
Marín
Ignacio
I
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, Spain. imarin@ibv.csic.es
van Egmond
Wouter N
WN
van Haastert
Peter J M
PJ
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002352:Carrier Proteins / Q000502:physiology*; D064550:Death-Associated Protein Kinases; D004023:Dictyostelium / Q000737:chemistry / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D018631:ras Proteins / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C022994:cyclic GMP-binding protein; D064550:Death-Associated Protein Kinases; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; D018631:ras Proteins