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| | The alignment of PAK1 mRNA to its genomic sequence. |
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| Description | The PAK1 gene contains 14 exons. The sizes of the exons 1-14 are 189, 100, 129, 147, 37, 119, 174, 63, 48, 112, 117, 99, 196, 137, and 86 bps. Exon 2 contains the translation initation ATG, and a few additional codons. Exon 13 contains the stop codon. Other features of the PAK1 gene, such as promoters or enhancer elements, have not been described. |
| Transcription | PAK1 expression is particularly high in the brain. Other tissues which have reasonably high levels of PAK1 expression include spleen and skeletal muscle. The mRNA size is 1945 bps. |
| Description | PAK1 is a highly conserved serine/threonine protein kinase of 545 amino acids and is a member of the PAK group of the STE20 family of serine/threonine protein kinases. Pak1 is active in a monomeric form; the non-active form is an autoinhibited homodimer. Pak1 contains a regulatory N-terminal regulatory domain and C-terminal catalytic domain The regulatory domain consists of a p21 GTPase-binding domain (PBD), an inhibitory domain (PID); five SH3-domains; and one non-classical SH3-binding site for the PIX family of proteins (PXP). Pak1 binds to activated forms of the GTPases Cdc42 and Rac. Pak1 homodimerizes through a motif adjacent to the p21-binding domain, and is autoinhibited. Upon binding to Cdc42 or Rac, Pak1 is activated and autophosphorylates. Pak1 has dozens of substrates, activating cytoskeletal and transcription pathways that enhance cell motility, proliferation, and survival. |
| Expression | PAK1 is highly expressed in epithelium of tongue and larynx and in thyroid gland, expression also found in central nervous system (brain). |
| Localisation | Under basal conditions, Pak1 localizes to the cytosol. Upon growth factor stimulation, Pak1 is recruited to the plasma membrane as well as the nucleus. |
| Function | Cell survival and proliferation |
| Homology | Similar to STE20 in budding yeast and PAK1 in fission yeast. Human PAK1 complements both these yeast genes. |
| Entity | Cancers |
| Disease | There is emerging evidence that the Pak family may play a key role in several human malignancies, including breast, ovarian, head and neck, colon, thyroid, and renal cancer. In human breast cancer, the expression level of Pak1 correlates with the tumor grade, with higher expression in less differentiated ductal carcinomas of the breast (grade III tumors) than in grade II and grade I tumors. Pak1 overexpression is also associated with tamoxifen resistance in breast cancer. In human tumors, Pak1 is not itself activated by mutation: rather, Pak1 is overexpressed by unknown mechanisms. Pak1 may also play a role in transformation by Kaposi's sarcoma-associated herpes virus, which induces Kaposi's sarcoma and primary effusion lymphomas. |
| Prognosis | Recently, it has been shown that the level of phosphorylated (activated) Pak1 Level in the cytoplasm correlates with shorter survival time in patients with glioblastoma. As noted above, Pak1 expression may also correlate with tamoxifen resistance in breast cancer. |
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