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Description
Cool/Pix proteins comprise a family of guanine nucleotide exchange factors (GEFs) localized to focal adhesions. The family consists of two isoforms, cool2/alphapix and cool1/betaPix, the latter having two splice variants that vary in their carboxy termini. Cool1/betaPix, like other GEFs, has a DH (Dbl homology) domain, which allows binding of small GTPases and GDP/GTP exchange, and a PH (Pleckstrin homology) domain, which is important in regulating subcellular localization. Cool1/betaPix also has an SH3 domain, which binds to the PAK kinase, a downstream effector of cdc42 and Rac. Phosphorylation of cool1/betaPix by PAK2 downstream of MAPK signaling alters the localization of a complex containing PAK2 and cool-1/betaPix, regulating formation of growth cones in response to growth factors. Growth factor induced activation of Rac1 via cool1/betaPix was later shown to occur independently of subcellular localization. Endothelin-1 stimulation of mesangial cells stimulates the protein kinase A (PKA) pathway, resulting in translocation of cool-1/betaPix and activation of cdc42.Synonyms: ARHGEF7, BETA-PIX, COOL1, DKFZp686C12170, DKFZp761K1021, KIAA0142, KIAA0412, Nbla10314, P50, P50BP, P85, P85COOL1, P85SPR, PAK3, PIXB