lation ▁or ▁by ▁up stream ▁kin ases . ▁ ▁To ▁date , ▁M AP 4 K 4 ▁has ▁been ▁found ▁to ▁be ▁expressed ▁in ▁all ▁t issue ▁types ▁with ▁a ▁relatively ▁more ▁pron ounced ▁expression ▁in ▁the ▁brain ▁and ▁test es . ▁Multiple ▁is o forms ▁of ▁M AP 4 K 4 ▁can ▁be ▁present ▁at ▁any ▁given ▁time ▁in ▁the ▁same ▁cell ▁but ▁the ▁abund ance ▁of ▁each ▁is o form ▁in ▁the ▁cell ▁diff ers ▁depending ▁on ▁the ▁cell - type ▁or ▁t issue - type . ▁ ▁E . g . ▁In ▁humans , ▁the ▁shorter ▁is o form ▁of ▁M AP 4 K 4 ▁is ▁pre domin antly ▁expressed ▁in ▁org ans ▁including ▁the ▁li ver , ▁pla cent a , ▁ske let al ▁mus cles ▁while ▁a ▁longer ▁is o form ▁is ▁expressed ▁in ▁the ▁brain ▁ ▁Inter actions ▁and ▁signal ing ▁ ▁T NF - α ▁ ▁Ev idence ▁from ▁m amm al ian ▁and ▁fly ▁studies ▁indicate ▁that ▁M AP 4 K 4 ▁is ▁involved ▁with ▁tum our ▁ne c ros is ▁factor ▁alpha ▁( T NF - α ) ▁and ▁its ▁c - j un ▁N - term inal ▁kin ase ▁( J N K ) ▁signal ing ▁path way . ▁M AP 4 K 4 ▁not ▁only ▁medi ates ▁T NF - α ▁signal ing ▁but ▁also ▁prom otes ▁its ▁expression ; ▁moreover , ▁T NF - α ▁can ▁elev ate ▁M AP 4 K 4 ▁expression ▁using ▁trans cription ▁factors ▁ ▁The ▁J