Mutation cytoplasmic

G proteins ras Point mutation Cytoplasm Multiple cancers including lung, colon, thyroid, pancreas, many leukemias... 

Btk (Bruton s tyrosine kinase) is a phosphatidylinositol 3 -kinase sensitive cytoplasmic tyrosine kinase. Germline loss of function mutations of Btk cause X-linked agammaglobulinaemia in human and X-linked immunodeficiency in mice. 

Disease-causing mutations are found in the cytoplasmic regulatory region of the (3 and y subunits of the epithelial sodium channel (ENaC) genes. In general, patients with Liddle s syndrome can be treated successfully with the ENaC inhibitor amiloride. 

Furthermore, if the antibiotic passes membranes through a specific port of entry, its mutational loss leads to resistance. The lack of the outer membrane protein OprD in P. aeruginosa causes resistance to the (3-lactam antibiotic imipenem. Fosfomycin passes the cytoplasmic membrane via an L-a-glycerol phosphate permease. This transport system is not essential for bacterial growth and therefore mutants with a reduced expression are frequently selected under therapy. 

Figure 52-7. Simplified scheme of the sequence of events involved in the causation of chronic granulomatous disease (MIM 306400). Mutations in any of the genes for the four polypeptides involved (two are components of cytochrome b55gand two are derived from the cytoplasm) can cause the disease. The polypeptide of 91 kDa is encoded by a gene in the X chromosome approximately 60% of cases of chronic granulomatous disease are X-linked, with the remainder being inherited in an autosomal recessive fashion.

Mutations in another region, the second cytoplasmic loop between M2 and M3 in Ca-ATPase of sarcoplasmic reticulum (Thr ->Ala, Gly -t Ala, and Glu Gln) also result in a complete loss of Ca-transport and Ca-ATPase activity associated with a dramatic reduction in the rate of phosphoenzyme turnover [96]. These mutations do not affect the affinity of the enzyme for Pj and therefore resemble the Pro mutants [123] in that they affect only the E1P-E2P conformational change and not the affinities for ATP, Ca or Pj. 

Studies of other members of the family have also added support to the topological model shown in the Fig. 3. In particular, chemical labelling of the native and mutated tetracycline transporter has confirmed the cytoplasmic location of the N-terminus and the loop connecting transmembrane helices 2 and 3 [231,232]. Protease digestion experiments on this protein have also provided preliminary evidence for the cyto-... 

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