SRC family kinases

SRC family kinases
Name	SRC family kinases

SRC family kinases

Introduction

SRC family kinases are a group of non-receptor tyrosine kinases historically linked to the discovery of viral oncogenes and cellular proto-oncogenes. Early research connected these kinases to laboratories and figures such as Theodor Boveri, J. Michael Bishop, Howard Temin, Harold Varmus, Max Delbrück, and institutions like the Cold Spring Harbor Laboratory, Rockefeller University, and the University of California, Berkeley. Their characterization involved techniques developed at facilities including the Francis Crick Institute, Wellcome Trust Sanger Institute, and the Max Planck Society, intersecting with broader projects like the Human Genome Project and collaborations among centers such as Massachusetts General Hospital and Johns Hopkins University.

Structure and Molecular Features

The canonical domain architecture was elucidated through structural biology groups at institutions like European Molecular Biology Laboratory, Stanford University, and Harvard Medical School. Crystallographic studies from teams at MRC Laboratory of Molecular Biology and University of Cambridge revealed conserved SH3, SH2, and kinase (SH1) domains, regulatory C-terminal tails, and unique N-terminal myristoylation signals characterized in reports from National Institutes of Health investigators. Comparative genomics efforts by consortiums including Ensembl and GenBank demonstrated conserved residues and motifs across species studied in collections at the Smithsonian Institution and American Museum of Natural History.

Family Members and Isoforms

Major family members were identified across laboratories at Columbia University, Yale University, and University of Pennsylvania and include several paralogs with tissue-specific expression cataloged by consortia like the GTEx Project and databases at European Bioinformatics Institute. Historical naming and variant studies involved researchers affiliated with University College London and Duke University. Isoform diversity and splice variants were mapped in studies linked to centers such as Cold Spring Harbor Laboratory Press and the Broad Institute.

Biological Functions and Signaling Pathways

Functional characterization emerged from collaborations among cell biology groups at MIT, Caltech, and UCSF, linking SRC family kinases to cytoskeletal regulation, cell adhesion, and growth factor signaling mediated via receptors studied at Mayo Clinic and Cleveland Clinic. Pathway mapping projects including those at EMBL-EBI and KEGG connected these kinases to cascades investigated by groups at Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute, with physiological roles examined in animal facilities at Rockefeller University and Salk Institute.

Regulation and Post-translational Modifications

Regulatory mechanisms were parsed by biochemical teams at Swiss Federal Institute of Technology Zurich and University of Tokyo, showing phosphorylation, myristoylation, and ubiquitination control described in reviews from Nature Reviews Molecular Cell Biology and Annual Review of Biochemistry editorial boards. Protein interaction networks compiled by STRING and experimental proteomics performed at Max Planck Institute for Biochemistry highlighted modulators identified by groups at Karolinska Institute and Imperial College London.

Roles in Development and Disease

Links between dysregulation and pathologies were pursued by clinical researchers at Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, and Royal Marsden Hospital, implicating SRC family kinases in oncogenesis, metastasis, and other diseases studied in cohorts from Framingham Heart Study and trials coordinated by National Cancer Institute. Animal model work at Wistar Institute and The Jackson Laboratory contributed to developmental phenotypes and disease models, while epidemiological and translational studies involved partnerships with World Health Organization initiatives and health systems like Kaiser Permanente.

Therapeutic Targeting and Inhibitors

Drug discovery efforts at pharmaceutical companies such as GlaxoSmithKline, Pfizer, Novartis, and Bristol-Myers Squibb brought SRC family kinase inhibitors into clinical development in collaboration with academic centers including University of Oxford and McGill University, with clinical trials registered through consortia like ClinicalTrials.gov and regulatory review by agencies such as the Food and Drug Administration and the European Medicines Agency. Structural-guided medicinal chemistry benefited from collaborations with research groups at Merck & Co., AstraZeneca, and university spin-outs from University of Cambridge and ETH Zurich.

Category:Protein kinases