PAK kinases are directly coupled to the PIX family of nucleotide exchange factors.
The PAK family of kinases are regulated through interaction with the small GTPases Cdc42 and Rac1, but little is known of the signaling components immediately upstream or downstream of these proteins. We have purified and cloned a new class of Rho-p21 guanine nucleotide exchange factor binding tightly through its N-terminal SH3 domain to a conserved proline-rich PAK sequence with a Kd of 24 nM. This PAK-interacting exchange factor (PIX), which is widely expressed and enriched in Cdc42- and Rac1-driven focal complexes, is required for PAK recruitment to these sites. PIX can induce membrane ruffling, with an associated activation of Rac1. Our results suggest a role for PIX in Cdc42-to-Rac1 signaling, involving the PIX/PAK complex.
Manser
E
E
Glaxo-IMCB Group, Institute of Molecular and Cell Biology, Singapore.
Loo
T H
TH
Koh
C G
CG
Zhao
Z S
ZS
Chen
X Q
XQ
Tan
L
L
Tan
I
I
Leung
T
T
Lim
L
L
D016475:3T3 Cells / Q000502:physiology; D000818:Animals; D000906:Antibodies; D019556:COS Cells / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000276:immunology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006150:Guanine Nucleotides / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D051419:Paxillin; D010750:Phosphoproteins / Q000032:analysis / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000201:enzymology; D014162:Transfection; D020764:cdc42 GTP-Binding Protein; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D018909:src Homology Domains / Q000235:genetics
D000906:Antibodies; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D006150:Guanine Nucleotides; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; C496063:Pxn protein, rat; D012333:RNA, Messenger; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins