Rac1 is a member of the Ras superfamily of small GTPases involved in signal
transduction pathways that induce the formation of lamellipodia, stimulate
cell proliferation and activate the JNK/SAPK protein kinase cascade, Here
we describe that amplification by RT-PCR of the entire Rac1 coding sequence
from a series of human adult and fetal tissues revealed beside the expecte
d Rac1 cDNA, a variant product which contained additional 57 nucleotides be
tween codons 75 and 76. This variant resulted in an in-frame insertion of 1
9 new amino acids immediately behind the switch II region, including two po
tential threonine phosphorylation sites for casein kinase II and protein ki
nase C, Primers designed within and downstream of the inserted nucleotide s
equence allowed isolation of a genomic clone with intronic consensus sequen
ces demonstrating that the insertion corresponds to a novel, yet undescribe
d exon 3b, This Rac1 splice variant, designated Rac1b, was predominantly id
entified in skin and epithelial tissues from the intestinal tract. Most not
ably, the expression of rac1b versus rad was found to be elevated in colore
ctal tumors at various stages of neoplastic progression, as compared to the
ir respective adjacent tissues. We suggest that the 19 amino acid-insertion
following the switch II region may create a novel effector binding site in
rac1b, and thus participate in signaling pathways related to the normal or
neoplastic growth of the intestinal mucosa.