Scambio, a novel guanine nucleotide exchange factor for Rho.
BACKGROUND
Small GTPases of the Rho family are critical regulators of various cellular functions including actin cytoskeleton organization, activation of kinase cascades and mitogenesis. For this reason, a major objective has been to understand the mechanisms of Rho GTPase regulation. Here, we examine the function of a novel protein, Scambio, which shares homology with the DH-PH domains of several known guanine nucleotide exchange factors for Rho family members.


RESULTS
Scambio is located on human chromosome 14q11.1, encodes a protein of around 181 kDa, and is highly expressed in both heart and skeletal muscle. In contrast to most DH-PH-domain containing proteins, it binds the activated, GTP-bound forms of Rac and Cdc42. However, it fails to associate with V14RhoA. Immunofluorescence studies indicate that Scambio and activated Rac3 colocalize in membrane ruffles at the cell periphery. In accordance with these findings, Scambio does not activate either Rac or Cdc42 but rather, stimulates guanine nucleotide exchange on RhoA and its close relative, RhoC.


CONCLUSIONS
Scambio associates with Rac in its activated conformation and functions as a guanine nucleotide exchange factor for Rho.
Curtis
Christina
C
Division of Hematology/Oncology, Section of Molecular Carcinogenesis, Childrens Hospital Los Angeles Research Institute and the Keck School of Medicine of the University of Southern California, Los Angeles, California 90027, USA. christina@rustycup.com
Hemmeryckx
Bianca
B
Haataja
Leena
L
Senadheera
Dinithi
D
Groffen
John
J
Heisterkamp
Nora
N
D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009132:Muscles / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D020662:Guanine Nucleotide Exchange Factors; C491480:scambio protein, human; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein