GAPs in growth factor signalling.
Approximately 2% of genes predicted by the sequenced human genome encode small GTPases and their regulators, highlighting the biological significance of regulated GTPase activity. Among the key GTPase regulators are the GTPase activating proteins (GAPs), which function to down-modulate active GTPases. Of the numerous identified GAPs, several have been implicated in signal transduction downstream of growth factors. In particular, GAPs for the Ras and Rho GTPases, which mediate a variety of receptor-transduced signals, appear to play an essential role in growth factor dependent GTPase regulation. Experimental studies of several of the GAPs have begun to elucidate mechanisms by which GAP activity is influenced by growth factor signaling, including direct phosphorylation, sub-cellular redistribution and protein degradation. Here, some of these mechanisms of GAP regulation in the context of signaling responses to growth factors are reviewed.
Bernards
Andre
A
Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
Settleman
Jeffrey
J
D001921:Brain / Q000378:metabolism; D015536:Down-Regulation; D020690:GTPase-Activating Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006133:Growth Substances / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D025542:Neurofibromin 1 / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020729:p120 GTPase Activating Protein / Q000378:metabolism; D020666:ras-GRF1
C074560:ARHGAP35 protein, human; C513043:ARHGAP5 protein, human; D020690:GTPase-Activating Proteins; D006133:Growth Substances; D020662:Guanine Nucleotide Exchange Factors; D025542:Neurofibromin 1; D009687:Nuclear Proteins; D010743:Phospholipids; C513039:RASGRF1 protein, human; D012097:Repressor Proteins; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020729:p120 GTPase Activating Protein; D020666:ras-GRF1