## 3 Hog Pathway in _Aspergillus nidulans_  
As in the case of _S. cerevisiae_, the HogA (SakA) pathway of _A. nidulans_ (Figure 1) is activated in the osmotic [13,14,46,47,48] and oxidative [46,47] response by the _A. nidulans_ Ssk1p ortholog, SskA. Interestingly, a _sakA_ null mutant presented only slight sensitivity to high osmolarity stress, indicating that osmoregulation in _A. nidulans_ differs from that described in yeast [14,46]. Other upstream components of this pathway are the Sln1p homolog, TcsB [49]; the Ypd1p ortholog, YpdA [14,48]; and also NikA, a dispensible Mak2-type histidine kinase in the osmotic stress response that has been demonstrated to transmit fungicide-induced stress signals such as those generated in the presence of fluidoxonil and iprodione [48,50] (Figure 1). A _tcsB_ deletion (_tcsB_) mutant did not present an osmosensitive phenotype [51] most likely due to redundancy of function with other histidine kinase genes present in _A. nidulans_ genome [48,52]. However, the _A. nidulans_ TcsB-YpdA-SskA system might have a role similar to that of Sln1p-Ypd1p-Ssk1p proteins in yeast [14]. A non-essential sensor kinase, TcsA, may be involved in condiation [53] however, a TcsA-YpdA-response regulator signalling pathway has not been demonstrated.  
Interestingly, it is likely that the Sho1p signaling pathway in _A. nidulans_ might not be involved in osmoregulation but instead may be carrying out other signaling functions [54]. _A. nidulans_ PbsB (homolog to _S. cerevisiae_ Pbs1p) lacks a typical Pro-rich motif necessary for the binding with Sho1p [14,55]. Furthermore, proteins such as ModA, a Cdc42p-like protein [56], similar to Sho1p, have a role in morphogenesis. SteC, similar to Ste11p, regulates sexual development [57]. Differently from yeast, _A. nidulans_ PbsB MAPKK activates another Hog1p ortholog, MpkC, not present in yeast. Although MpkC is not necessary for osmoregulation, overexpression of _mpkC_ suppresses the slight high-osmolarity sensitivity of _hogA_ strains [14]. An _A. nidulans_ orthologique of _S. cerevisiae_ Skn7p, SrrA, plays a role in both oxidative stress and osmotic stress resistance [47,48].  
Little is known about SakA and YpdA import/export to the nucleus, although putative orthologues of Gsp1p (RanA), Nmd5p importin and Crm1p (KapK) export factor have be identified [12]. Dephosphorylation of HogA/SakA in _A. nidulans_ is mainly unknown, except for the up-regulation of _ptpA_ (encoding a putative protein phosphatase) when the fungus is exposed to osmotic stress [13]. Several SakA-dependent regulators have been identified, such as RpdA (Rpd3p ortholog), Atfa(putative ortholog of _S. pombe_ Atf1) [58, 59], and RcoA (_S. cerevisiae_ Tup1 ortholog). Msn2p/Msn4p-type protein, MsnA, has been found in _A. nidulans_, and was shown to be induced by different types of stress [13]. In _A. nidulans_, potential target genes of SakA and SrrA (_S. cerevisiae_ Skn7p homolog) includes _gfdB_ (_S. cerevisiae_ GPD2 ortholog) [13, 60] and _enaA_[13].  
The process of osmotic adaptation by activation of the HOG pathway, in both yeast and filamentous fungi, results in the biosynthesis and accumulation of compatible molecules such as proline, trehalose, polyols and glycerol to counterbalance the osmotic pressure and prevent loss of water. In _A. nidulans_, SskA (_S. cerevisiae_ Ssk1p homolog) regulates the expression of genes involved in conidial tolerance to stress, including genes involved in glycerol and trehalose metabolism (_gfdA_ and _gfdB_, glycerol-3-phosphate dehydrogenases; _gldB_, glycerol dehydrogenase; _tpsA_, trehalose-6-phosphate synthase; _orIA_, trehalose-6-phosphate phosphatase; _treB_, neutral trehalose) [13, 61, 62, 63, 64, 65].