?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F27697%2F&rft.title=Optical+Control+of+Signal+Transduction+and+Other+Cellular+Processes&rft.creator=Brown%2C+Kalyn+A&rft.description=Nature+uses+precise+spatio-temporal+control+to+maintain+proper+cellular+function.+Being+able+to+replicate+this+control+is+an+important+step+in+investigating+proteins.+The+research+presented+here+uses+photo-labile+%E2%80%9Ccaging%E2%80%9D+groups+and+light+to+control+protein+function+including+signaling+cascades%2C+protein+localization+and+dimerization.+Cell+signaling+is+an+essential+process+that+allows+cells+to+respond+to+extracellular+stimuli.+Four+kinases%2C+ERK2%2C+p38%CE%B1%2C+JNK1+and+PAK1%2C+were+targeted+to+optochemically+control+signal+transduction.+ERK2%2C+p38%CE%B1%2C+and+JNK1+are+MAP+kinases+that+are+implicated+in+cell+proliferation%2C+apoptosis%2C+motility%2C+and+differentiation.+PAK1+is+a+serine%2Fthreonine+kinase+that+affects+focal+adhesion+dynamic+and+action+reorganization.+Incorporation+of+a+photocaged+lysine+into+the+ATP+binding+pocket+of+PAK1+allowed+for+optical+control+of+PAK1+kinase+activity+and+paxillin+focal+adhesions.++Ras+GTPases+are+membrane+bound+molecular+switches+involved+in+various+pathways+that+convert+stimuli+into+a+cellular+response.+Membrane+localization+of+Ras+GTPases+is+determined+by+the+C-terminal+CaaX+domain.+Within+the+CaaX+domain%2C+cysteine+residues+are+modified+by+the+addition+of+a+farnesyl+group+and+two+palmitoyl+groups.+Ultimately%2C+photochemical+control+of+membrane+localization+by+CaaX+domain+signaling+was+used+to+determine+the+kinetics+of+CaaX+domain+processing.+Src+family+tyrosine+kinases+are+involved+in+cell+proliferation%2C+cytoskeletal+alterations%2C+differentiation%2C+survival%2C+adhesion%2C+and+migration+and+are+localized+to+the+membrane+through+the+modification+of+a+SH4+domain+with+myristoylation+and+palmitoylation.+Optochemical+control+of+SH4+domain+mediated+membrane+localization+was+not+achieved.+Finally%2C+the+dimerization+of+FKBP12+and+FRB+was+photochemically+controlled+by+the+development+of+a+photo-cleavable+rapamycin+dimer.+Rapamycin+heterodimerizes+FKBP12+and+FRB+and+has+been+exploited+as+a+research+tool+in+a+wide+array+of+cellular+processes.+Photochemical+control+of+protein+localization+and+dimerization+allows+for+precise+spatial+and+temporal+control+over+these+processes%2C+which+will+lend+to+the+development+of+useful+biological+tools.&rft.date=2016-06-01&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F27697%2F1%2FKalyn_Brown_ETD_2016_revised.pdf&rft.identifier=++Brown%2C+Kalyn+A++(2016)+Optical+Control+of+Signal+Transduction+and+Other+Cellular+Processes.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++