High impact information on KIFAP3

• The interaction of APC with KAP3 was required for its accumulation in clusters, and mutant APCs derived from cancer cells were unable to accumulate efficiently in clusters [1].
• We show here that APC interacts with the kinesin superfamily (KIF) 3A-KIF3B proteins, microtubule plus-end-directed motor proteins, through an association with the kinesin superfamily-associated protein 3 (KAP3) [1].
• Conversely, SmgGDS nuclear accumulation is diminished by interactions with RhoA [2].
• Novel mechanism of the co-regulation of nuclear transport of SmgGDS and Rac1 [2].
• An SmgGDS nuclear export signal sequence that we identified promotes SmgGDS nuclear export [2].

Biological context of KIFAP3

• We isolated here a SMAP-interacting protein from a human brain cDNA library, identified it to be a human homolog of Xenopus XCAP-E (Xenopus chromosome-associated polypeptide), a subunit of condensins that regulate the assembly and structural maintenance of mitotic chromosomes, and named it HCAP (Human chromosome-associated polypeptide) [3].
• We have isolated here an Smg GDS-interacting protein from a human brain cDNA library by use of the yeast two-hybrid method and named it SMAP (Smg GDS-associated protein) [4].
• Searches for sequence homology to SMAP revealed that SMAP was significantly homologous to sea urchin SpKAP115, suggesting that SMAP is a mammalian counterpart of SpKAP115 or its related protein [4].
• SMAP was tyrosine phosphorylated by v-Src, and this phosphorylation reduced the affinity of SMAP for Smg GDS [4].
• In the chromosome 1 locus, a strong candidate gene, encoding the kinesin-associated protein 3 (KIF3AP) was not mutated, based on SSCP/heteroduplex analysis and direct sequencing [5].

Anatomical context of KIFAP3

• Tissue and subcellular distribution analyses indicated that SMAP was ubiquitously expressed and highly concentrated at the endoplasmic reticulum area [4].
• Microinjection of SmgGDS cDNA into CHO cells stably expressing HA-RhoA causes HA-RhoA to be excluded from the nucleus and cell junctions, similar to the distribution of RhoA(Asn-19) [6].
• Similarly to previously identified Rap GEFs, C3G and Smg GDS, each of the newly identified exchange factors promoted the activation of Elk-1 in the LNCaP prostate tumor cell line where B-Raf can couple Rap1 to the extracellular receptor-activated kinase cascade [7].

Associations of KIFAP3 with chemical compounds

• SMAP, an Smg GDS-associating protein having arm repeats and phosphorylated by Src tyrosine kinase [4].
• Unique in vivo associations with SmgGDS and RhoGDI and different guanine nucleotide exchange activities exhibited by RhoA, dominant negative RhoA(Asn-19), and activated RhoA(Val-14) [6].
• Polymerase chain reaction (PCR) amplification using primers within the coding sequences of each gene revealed that the KAP2 and KAP3 genes are linked on the same chromosomal DNA and are separated by a 1.8 kb intergenic region containing several long homopolymer tracts [8].

Physical interactions of KIFAP3

• SmgGDS co-precipitates minimally with wild-type RhoA and does not detectably associate with RhoA(Val-14) [6].

Regulatory relationships of KIFAP3

• Moreover, recombinant Smg GDS failed to stimulate GTP-dependent PLD activity [9].

Other interactions of KIFAP3

• Nor did the two other microtubule associated proteins, MAP4 or KAP3, which is thought to link APC to kinesin motor proteins, associate with the 60S complex [10].
• The stimulatory exchange factor, Smg GDS, which is active on Rho and Rac, could be partially separated from the PLD-stimulating factor(s) by gel-permeation chromatography [9].
• Our findings indicate that the expression of RhoA(Asn-19) may specifically inhibit signaling pathways that rely upon the SmgGDS-dependent activation of RhoA [6].
• Dominant negative RhoA(Asn-19) co-precipitates with the guanine nucleotide exchange factor (GEF) SmgGDS but does not detectably interact with other expressed GEFs, such as Ost or Dbl [6].
• These properties of Dbl were partly different from those of Smg GDS, another GEP which is active not only on the rho family members but also on Ki-Ras and Rap1 and is active only on their lipid-modified form [11].

References